WO2007117398B1 - Non-peptidic molecules for detecting and treating tumors - Google Patents
Non-peptidic molecules for detecting and treating tumorsInfo
- Publication number
- WO2007117398B1 WO2007117398B1 PCT/US2007/008215 US2007008215W WO2007117398B1 WO 2007117398 B1 WO2007117398 B1 WO 2007117398B1 US 2007008215 W US2007008215 W US 2007008215W WO 2007117398 B1 WO2007117398 B1 WO 2007117398B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- improved
- subject
- group
- tumors
- Prior art date
Links
- 206010028980 Neoplasm Diseases 0.000 title claims abstract 21
- 230000002378 acidificating effect Effects 0.000 claims abstract 25
- 230000006378 damage Effects 0.000 claims abstract 5
- 230000005855 radiation Effects 0.000 claims abstract 4
- 239000000203 mixture Substances 0.000 claims 41
- 239000002253 acid Substances 0.000 claims 12
- 239000000126 substance Substances 0.000 claims 12
- 150000001732 carboxylic acid derivatives Chemical group 0.000 claims 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims 6
- 239000007864 aqueous solution Substances 0.000 claims 6
- 210000000170 cell membrane Anatomy 0.000 claims 6
- 230000005251 gamma ray Effects 0.000 claims 6
- 239000002243 precursor Substances 0.000 claims 6
- 210000002700 urine Anatomy 0.000 claims 6
- 239000002245 particle Substances 0.000 claims 5
- 125000003118 aryl group Chemical group 0.000 claims 4
- 230000015572 biosynthetic process Effects 0.000 claims 4
- 210000004027 cell Anatomy 0.000 claims 4
- PDWUPXJEEYOOTR-UHFFFAOYSA-N 2-[(3-iodophenyl)methyl]guanidine Chemical compound NC(=N)NCC1=CC=CC(I)=C1 PDWUPXJEEYOOTR-UHFFFAOYSA-N 0.000 claims 3
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 claims 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims 3
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 claims 3
- 229960000571 acetazolamide Drugs 0.000 claims 3
- 239000000872 buffer Substances 0.000 claims 3
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims 3
- 229960000830 captopril Drugs 0.000 claims 3
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 claims 3
- 239000008103 glucose Substances 0.000 claims 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims 3
- 239000003112 inhibitor Substances 0.000 claims 3
- 230000002438 mitochondrial effect Effects 0.000 claims 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims 3
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 3
- 229940124549 vasodilator Drugs 0.000 claims 3
- 239000003071 vasodilator agent Substances 0.000 claims 3
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims 2
- RYXHOMYVWAEKHL-OUBTZVSYSA-N astatine-211 Chemical compound [211At] RYXHOMYVWAEKHL-OUBTZVSYSA-N 0.000 claims 2
- KIPSRYDSZQRPEA-UHFFFAOYSA-N 2,2,2-trifluoroethanamine Chemical compound NCC(F)(F)F KIPSRYDSZQRPEA-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 1
- WKBOTKDWSSQWDR-OIOBTWANSA-N Bromine-77 Chemical compound [77Br] WKBOTKDWSSQWDR-OIOBTWANSA-N 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 1
- 150000001204 N-oxides Chemical class 0.000 claims 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 1
- CPELXLSAUQHCOX-AHCXROLUSA-N ac1l4zwb Chemical compound [76BrH] CPELXLSAUQHCOX-AHCXROLUSA-N 0.000 claims 1
- 125000005262 alkoxyamine group Chemical group 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- DFNYGALUNNFWKJ-UHFFFAOYSA-N aminoacetonitrile Chemical compound NCC#N DFNYGALUNNFWKJ-UHFFFAOYSA-N 0.000 claims 1
- 229910052789 astatine Inorganic materials 0.000 claims 1
- RYXHOMYVWAEKHL-UHFFFAOYSA-N astatine atom Chemical compound [At] RYXHOMYVWAEKHL-UHFFFAOYSA-N 0.000 claims 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 1
- CPELXLSAUQHCOX-NJFSPNSNSA-N bromine-82 Chemical compound [82BrH] CPELXLSAUQHCOX-NJFSPNSNSA-N 0.000 claims 1
- CPELXLSAUQHCOX-AKLPVKDBSA-N bromine-83 Chemical compound [83BrH] CPELXLSAUQHCOX-AKLPVKDBSA-N 0.000 claims 1
- 229910052794 bromium Inorganic materials 0.000 claims 1
- 239000004202 carbamide Substances 0.000 claims 1
- DMSZORWOGDLWGN-UHFFFAOYSA-N ctk1a3526 Chemical compound NP(N)(N)=O DMSZORWOGDLWGN-UHFFFAOYSA-N 0.000 claims 1
- 229910052731 fluorine Inorganic materials 0.000 claims 1
- 239000011737 fluorine Substances 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- XMBWDFGMSWQBCA-CONNIKPHSA-N iodane Chemical compound [135IH] XMBWDFGMSWQBCA-CONNIKPHSA-N 0.000 claims 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 1
- 125000000565 sulfonamide group Chemical group 0.000 claims 1
- 125000000129 anionic group Chemical group 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
One of the most universal characteristics of malignant tumors is their acidity. Onco-tools are small non-peptide synthetic molecules designed to exploit this acidity for early detection and destruction of tumors. Each onco-tool has a structure which is anionic and hydrophilic at pH 7.4 and so repels from the negatively-charged surfaces of cells in normal tissues. When an onco-tool enters an acidic environment, such as in a tumor, a portion of the onco-tool molecules switch to their non-ionic lipophilic form which is designed to enter cells, such as cells in acidic areas of tumors. Prior to use of an onco-tool, a selected radioisotope is linked to the onco-tool. If that radioisotope emits radiation which can be detected outside the body, then the onco-tool can serve for detecting tumors. If that radioisotope emits radiation effective to kill cells, then the onco-tool can serve for treating tumors.
Claims
1. A precursor structure that can be readily converted to a composition that is preferentially sequestered in acidic areas, which may be in tumors in a living subject, where the composition (i) has the property of existing largely in a negatively-charged water-soluble form in aqueous solution at pH 7.4, but in acidic areas below pH 7.0 a significant portion of the molecules of the composition switch to a non-ionic form effective to enter a lipophilic phase, which may be a cell membrane, and (ii) includes a cargo component which can report its presence by emitting a photon, a gamma ray (high-energy photon), or a positron, and/or which can cause damage to cells in the area where it is sequestered, wherein the improvement comprises:
an improved precursor structure that by addition of a radiohalogen can be converted to an improved composition that is preferentially sequestered with improved specificity in acidic areas, which contains
(a) at least two acid moieties;
(b) at least one of the acid moieties is incorporated in an internally H-bondable component having the properties i) the acid moiety is a carboxylic acid moiety directly linked to a ring structure, ii) the ring structure is non-aromatic and is selected from the group consisting of a 4-membered ring, a 5-membered ring, and a 6-membered ring, iii) also attached to the ring structure is an H-bond acceptor moiety which has a pKa of less than 7 and which in its non-ionic form has a structure which cannot serve as an H-bond donor moiety and where the atom which serves as the acceptor in the H-bond is selected from the group consisting of directly linked to the ring structure, and linked through one atom to the ring structure, wherein the carboxylic acid moiety and the H-bond acceptor moiety are positioned and oriented such that they are compatible with formation of an internal H-bond; and, (c) at least one cargo component in a precursor form which is effective to readily and stably bind a radiohalogen; and which lacks
(d) a sulfonamide moiety ( R1SO2NR2R3)
2. The improved precursor structure of Claim 1 , wherein the at least one cargo component in a precursor form includes a tri-alkyl tin moiety.
3. The improved precursor structure of Claim 2, wherein the best mode structure is:
4. A composition that is preferentially sequestered in acidic areas, which may be in tumors in a living subject, where the composition (i) has the property of existing largely in a negatively-charged water-soluble form in aqueous solution at pH 7.4, but in acidic areas below pH 7.0 a significant portion of the molecules of the composition switch to a non-ionic form effective to enter a lipophilic phase, which may be a cell membrane, and (ii) includes a cargo component which can report its presence by emitting a photon, a gamma ray (high- energy photon), or a positron, and/or which can cause damage to cells in the area where it is sequestered, wherein the improvement comprises:
an improved composition that is preferentially sequestered with improved specificity in acidic areas, which contains (a) at least two acid moieties;
(b) at least one of the acid moieties is incorporated in an internally H-bondable component having the properties i) the acid moiety is a carboxylic acid moiety directly linked to a ring structure, ii) the ring structure is non-aromatic and is selected from the group consisting of a 4-membered ring, a 5-membered ring, and a 6-membered ring, iii) also attached to the ring structure is an H-bond acceptor moiety which has a pKa of less than 7 and which in its non-ionic form has a structure which cannot serve as an H-bond donor moiety and where the atom which serves as the acceptor in the H-bond is selected from the group consisting of directly linked to the ring structure, and linked through one atom to the ring structure, wherein the carboxylic acid moiety and the H-bond acceptor moiety are positioned and oriented such that they are compatible with formation of an internal H-bond; and,
(c) at least one cargo component which contains a radiohalogen.
5. The improved composition of Claim 4, wherein at least one cargo component contains a radiohalogen which is selected from the group of halogen types consisting of: Fluorine, Bromine, Iodine, and Astatine.
6. The improved composition of Claim 5, wherein the H-bond acceptor moiety in at least one internally H-bondable component is selected from the group consisting of:
(a) an amide;
(b) a trifluoroethylamine;
(c) a cyanomethylamine;
(d) an alkoxyamine;
(e) an N-oxide;
(f) an imidazole;
(g) an aniline;
(h) a phosphoramide; and, (i) a urea.
7. The improved composition of Claim 6, wherein at least one internally H-bondable component has a structure selected from the group consisting of: 
8. The improved composition of Claim 7, wherein the molecular structure is selected from the group consisting of:
X = radiohalogen 
9. The improved composition of Claim 8, wherein the best mode structure is:
10. A composition for detecting the presence of acidic areas, which may be in tumors in a living subject, where the composition (i) has the property of existing largely in a negatively- charged water-soluble form in aqueous solution at pH 7.4, but in acidic areas below pH 7.0 a significant portion of the molecules of the composition switch to a non-ionic form effective to enter a lipophilic phase, which may be a cell membrane in a biological tissue, and (ii) includes a cargo component which can report its presence by emitting a photon, gamma ray (high-energy photon), or positron from the area where it is sequestered, wherein the improvement comprises:
an improved composition for detecting with improved specificity the presence of acidic areas, which contains
(a) at least two acid moieties;
(b) at least one of the acid moieties is incorporated in an internally H-bondable component having the properties i) the acid moiety is a carboxylic acid moiety directly linked to a ring structure, ii) the ring structure is non-aromatic and is selected from the group consisting of a 4-membered ring, a 5-membered ring, and a 6-membered ring, iii) also attached to the ring structure is an H-bond acceptor moiety which has a pKa of less than 7 and which in its non-ionic form has a structure which cannot serve as an H-bond donor moiety and where the atom which serves as the acceptor in the H-bond is selected from the group consisting of directly linked to the ring structure, and linked through one atom to the ring structure wherein the carboxylic acid moiety and the H-bond acceptor moiety are positioned and oriented such that they are compatible with formation of an internal H-bond; and,
(c) at least one cargo component which contains a radiohalogen that emits radiation of a type selected from the group consisting of i) a gamma ray, ii) a positron, and iii) a positron and a gamma ray.
11. The improved composition of Claim 10, wherein the radiohalogen is selected from the group consisting of: Bromine-76, Bromine-77, lodine-123, lodine-124, and lodine-131.
12. The improved composition of Claim 11 , wherein the best mode structure is:
13. A method for detecting acidic areas in a subject, where the acidic areas may be in tumors, by
(a) providing a composition which
(i) has the property of existing largely in a negatively-charged water-soluble form in aqueous solution at pH 7.4, but in acidic areas below pH 7.0 a significant portion of the molecules of the composition switch to a non-ionic form effective to enter a lipophilic phase, which may be a cell membrane in a biological tissue, and (ii) includes a cargo component which can report its presence by emitting a photon, a gamma ray (high-energy photon), or a positron from the area where it is sequestered,
(b) introducing the provided composition into the subject,
(c) waiting for a period of time in the range of 10 minutes to 48 hours, and
(d) assessing the subject with equipment effective to detect the emission from the cargo component of the provided composition, wherein the improvement comprises:
an improved method for detecting with improved specificity acidic areas in a subject, wherein the provided composition is the composition of Claim 10, and the subject is assessed with equipment effective to detect gamma rays.
14. The improved method of Claim 13, wherein the improved method is used for assessing a living subject for the presence of tumors containing acidic areas.
15. The improved method of Claim 13, wherein the improved method further comprises: first treating the subject with
(a) at least one substance effective to increase the pH of the subject's urine; and,
(b) at least one substance effective to decrease the pH in tumors.
16. The improved method of Claim 15, wherein at least one substance effective to increase the pH of the subject's urine is selected from the group consisting of:
(a) a carbonic anhydrase inhibitor acetazolamide; and,
(b) a buffer sodium bicarbonate.
17. The improved method of Claim 15, wherein at least one substance effective to decrease the pH in tumors is selected from the group consisting of:
(a) glucose;
(b) the mitochondrial inhibitor meta-iodobenzylguanidine; and,
(c) the vasodilator captopril.
18. A composition for treating acidic areas, which may be in tumors in a living subject, where the composition (i) has the property of existing largely in a negatively-charged water-soluble form in aqueous solution at pH 7.4, but in acidic areas below pH 7.0 a significant portion of the molecules of the composition switch to a non-ionic form effective to enter a lipophilic phase, which may be a cell membrane in a biological tissue, and (ii) includes a cargo component which can cause damage to cells in the area where it is sequestered, wherein the improvement comprises:
an improved composition for treating with improved specificity acidic areas, which contains
(a) at least two acid moieties;
(b) at least one of the acid moieties is incorporated in an internally H-bondable component having the properties i) the acid moiety is a carboxylic acid moiety directly linked to a ring structure, ii) the ring structure is non-aromatic and is selected from the group consisting of a 4-membered ring, a 5-membered ring, and a 6-membered ring, iii) also attached to the ring structure is an H-bond acceptor moiety which has a pKa of less than 7 and which in its non-ionic form has a structure which cannot serve as an H-bond donor moiety and where the atom which serves as the acceptor in the H-bond is selected from the group consisting of directly linked to the ring structure, and linked through one atom to the ring structure, wherein the carboxylic acid moiety and the H-bond acceptor moiety are positioned and oriented such that they are compatible with formation of an internal H-bond; and,
(c) at least one cargo component which contains a radiohalogen that emits radiation of a type selected from the group consisting of i) an alpha particle, and ii) a beta particle.
19. The improved composition of Claim 18, wherein the radiohalogen emits an alpha particle and is Astatine-211.
20. The improved composition of Claim 19, wherein the best mode structure is:
21. The improved composition of Claim 18, wherein the radiohalogen emits a beta particle and is selected from the group consisting of: Bromine-82, Bromine-83, lodine-130, lodine- 131, lodine-132, lodine-133, and Iodine 135.
22. A method for treating acidic areas in a subject, where the acidic areas may be in tumors, by
(a) providing a composition
(i) with the property of existing largely in a negatively-charged water-soluble form in aqueous solution at pH 7.4, but in acidic areas below pH 7.0 a significant portion of the molecules of the composition switch to a non-ionic form effective to enter a lipophilic phase, which may be a cell membrane in a biological tissue, and
(ii) which includes a cargo component which can cause damage to cells in the area where it is sequestered, and
(b) introducing the provided composition into the subject, wherein the improvement comprises:
an improved method for treating with improved specificity acidic areas in a subject, wherein the provided composition is the composition of Claim 18.
23. The improved method of Claim 22, wherein the improved method is used for treating a living subject who has one or more tumors containing acidic areas.
24. The improved method of Claim 22, wherein the improved method further comprises: first treating the subject with
(a) at least one substance effective to increase the pH of the subject's urine; and,
(b) at least one substance effective to decrease the pH in tumors.
25. The improved method of Claim 24, wherein at least one substance effective to increase the pH of the subject's urine is selected from the group consisting of:
(a) the carbonic anhydrase inhibitor acetazolamide; and,
(b) the buffer sodium bicarbonate.
26. The improved method of Claim 24, wherein at least one substance effective to decrease the pH in tumors is selected from the group consisting of:
(a) glucose;
(b) the mitochondrial inhibitor meta-iodobenzylguanidine; and,
(c) the vasodilator captopril.
27. The improved method of Claim 22, wherein at least two compositions of Claim 18 are provided and are introduced into the subject, where one provided composition of Claim 18 contains the radiohalogen Astatine-211 , and where a second provided composition of Claim 18 contains a radiohalogen which emits a beta particle.
28. The improved method of Claim 27, wherein the best mode provided compositions are:
29. The improved method of Claim 27, wherein the method is used for treating a living subject who has one or more tumors containing acidic areas.
30. The improved method of Claim 27, wherein the improved method further comprises: first treating the subject with
(a) at least one substance effective to increase the pH of the subject's urine; and,
(b) at least one substance effective to decrease the pH in tumors.
31. The improved method of Claim 30, wherein at least one substance effective to increase the pH of the subject's urine is selected from the group consisting of:
(a) the carbonic anhydrase inhibitor acetazolamide; and,
(b) the buffer sodium bicarbonate.
32. The improved method of Claim 30, wherein at least one substance effective to decrease the pH in tumors is selected from the group consisting of:
(a) glucose;
(b) the mitochondrial inhibitor meta-iodobenzylguanidine; and, (C) the vasodilator captopril.
Priority Applications (12)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP07754699A EP1998760A2 (en) | 2006-03-30 | 2007-03-25 | Non peptidic molecules for detecting and treating tumors |
| AU2007235575A AU2007235575A1 (en) | 2006-03-30 | 2007-03-30 | Non-peptidic molecules for detecting and treating tumors |
| BRPI0710026-4A BRPI0710026A2 (en) | 2006-03-30 | 2007-03-30 | precursor structure, compositions and methods for detecting and treating acidic areas in an individual |
| MX2008012282A MX2008012282A (en) | 2006-03-30 | 2007-03-30 | Non-peptidic molecules for detecting and treating tumors. |
| PCT/US2007/008215 WO2007117398A2 (en) | 2006-03-30 | 2007-03-30 | Non-peptidic molecules for detecting and treating tumors |
| JP2009503073A JP2009536152A (en) | 2006-03-30 | 2007-03-30 | Non-peptide molecules for detecting and treating tumors |
| CA002647502A CA2647502A1 (en) | 2006-03-30 | 2007-03-30 | Onco-tool compositions and methods of use for detecting and treating tumors |
| MX2009010621A MX2009010621A (en) | 2007-03-30 | 2007-09-29 | Non-peptidic molecules for detecting and treating tumors. |
| PCT/US2007/021002 WO2008121126A1 (en) | 2007-03-30 | 2007-09-29 | Non-peptidic molecules for detecting and treating tumors |
| AU2007350326A AU2007350326A1 (en) | 2007-03-30 | 2007-09-29 | Non-peptidic molecules for detecting and treating tumors |
| CA002682567A CA2682567A1 (en) | 2007-03-30 | 2007-09-29 | Non-peptidic molecules for detecting and treating tumors |
| CR11069A CR11069A (en) | 2007-03-30 | 2009-10-19 | NON-PEPTIDIC MOLECULES FOR THE DETECTION AND TREATMENT OF TUMORS |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11/395,487 | 2006-03-30 | ||
| US11/395,487 US20070231256A1 (en) | 2006-03-30 | 2006-03-30 | Compositions and methods for detecting and treating tumors containing acidic areas |
| US11/449,495 | 2006-06-07 | ||
| US11/449,508 | 2006-06-07 | ||
| US11/449,495 US8084610B2 (en) | 2006-06-07 | 2006-06-07 | Compositions and methods for detecting and treating tumors containing acidic areas |
| US11/449,508 US20080124274A1 (en) | 2006-06-07 | 2006-06-07 | Compositions and methods for detecting and treating tumors containing acidic areas |
| PCT/US2007/008215 WO2007117398A2 (en) | 2006-03-30 | 2007-03-30 | Non-peptidic molecules for detecting and treating tumors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2007117398A2 WO2007117398A2 (en) | 2007-10-18 |
| WO2007117398A3 WO2007117398A3 (en) | 2007-12-06 |
| WO2007117398B1 true WO2007117398B1 (en) | 2008-02-07 |
Family
ID=41343282
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2007/008215 WO2007117398A2 (en) | 2006-03-30 | 2007-03-30 | Non-peptidic molecules for detecting and treating tumors |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP1998760A2 (en) |
| JP (1) | JP2009536152A (en) |
| AU (1) | AU2007235575A1 (en) |
| CA (1) | CA2647502A1 (en) |
| MX (1) | MX2008012282A (en) |
| WO (1) | WO2007117398A2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2007350326A1 (en) * | 2007-03-30 | 2008-10-09 | James E. Summerton | Non-peptidic molecules for detecting and treating tumors |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
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| AU2001265111A1 (en) * | 2000-05-30 | 2001-12-11 | Guilford Pharmaceuticals Inc. | Benzenedicarboxylic acid derivatives |
| US7491718B2 (en) * | 2002-10-08 | 2009-02-17 | Abbott Laboratories | Sulfonamides having antiangiogenic and anticancer activity |
| EP1615667A2 (en) * | 2003-04-11 | 2006-01-18 | Novo Nordisk A/S | Combinations of an 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist |
| US7285529B2 (en) * | 2005-02-28 | 2007-10-23 | Gene Tools, Llc | Embedder compositions and methods for detecting and killing cells in acidic areas of tumors |
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| MX2008012282A (en) | 2008-11-12 |
| CA2647502A1 (en) | 2007-10-18 |
| EP1998760A2 (en) | 2008-12-10 |
| AU2007235575A1 (en) | 2007-10-18 |
| JP2009536152A (en) | 2009-10-08 |
| WO2007117398A3 (en) | 2007-12-06 |
| WO2007117398A2 (en) | 2007-10-18 |
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