WO1999016787A1 - Agonistes de mort cellulaire - Google Patents

Agonistes de mort cellulaire Download PDF

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Publication number
WO1999016787A1
WO1999016787A1 PCT/US1998/019765 US9819765W WO9916787A1 WO 1999016787 A1 WO1999016787 A1 WO 1999016787A1 US 9819765 W US9819765 W US 9819765W WO 9916787 A1 WO9916787 A1 WO 9916787A1
Authority
WO
WIPO (PCT)
Prior art keywords
seq
leu
bcl
polypeptide
domain
Prior art date
Application number
PCT/US1998/019765
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English (en)
Other versions
WO1999016787A9 (fr
Inventor
Stanley J. Korsmeyer
Original Assignee
Washington University
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Washington University filed Critical Washington University
Priority to AU94028/98A priority Critical patent/AU9402898A/en
Publication of WO1999016787A1 publication Critical patent/WO1999016787A1/fr
Publication of WO1999016787A9 publication Critical patent/WO1999016787A9/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/435—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • C07K14/46—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
    • C07K14/47—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
    • C07K14/4701—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals not used
    • C07K14/4747—Apoptosis related proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy

Definitions

  • Yet another aspect of the invention provides polynucleotides encoding a BH3 polypeptide of no more than 50 amino acids having cell death agonist activity and comprising a BH3 domain of a pro-apoptotic BCL-2 family member.
  • the invention also provides polynucleotides encoding BH3 domain peptides of about five to eight contiguous amino acids from SEQ ID NO:40, or a conservatively substituted variant thereof. These polynucleotide may be used to transfect a target cell for expression of the BH3 polypeptide to promote death of the target cell.
  • the BH3 polypeptide or BH3 domain peptide can be administered to the target cell by transfecting the cell with an expression vector which comprises a polynucleotide encoding the BH3 polypeptide or BH3 domain peptide.
  • BAD- deficient murine embryonic fibroblasts MEF- deficient murine embryonic fibroblasts.
  • DNA fragments encoding for full-length BAD or truncated BAD proteins (1-181, 1-141, 127-204, and full-length with a deletion from 142 to 165) (Fig. 6A) and engineered to contain BamHI and EcoRI restriction sites were inserted into pcDNA3 ( Invitrogen ) , downstream of T7 and CMV promoters.
  • MEF cells were allowed to grow to about 80% confluence in 12-well plates before transfection.
  • the recombinant pSFFV expression vectors encoding the wild-type BAD and the BAD mutants described in Example 3 were electroporated into the murine hematopoietic cell line FL5.12 BCL-X L , which overexpresses BCL-X L .
  • Clones expressing similar levels of WT and mutant BAD proteins as well as BCL-X L were identified by probing Western blots of cell lysates with either a rabbit polyclonal anti-BAD antibody (#10929, described in Yang et al.. Cell 80: 285-291, 1995) (Fig. 7B, upper panel) or a rabbit polyclonal anti-BCL-XL antibody (13.6, described in Boise et al., Immunity 3 : 87-98, 1995) (Fig. 7B, lower panel ) .
  • Example 10 This example demonstrates that small BH3-containing BAX and BID fragments fused to a tat-peptide can promote cell death.
  • Example 11 This example demonstrates cell viability exposed illustrates the kinetics and dose-response relationship of cell death induced by Tat-BH3 polypeptides.
  • Tat-BAX( 53-76) Tat- BAX( 67-71)
  • Tat BID( 81-100) or their corresponding BH3 mutant derivatives were added at a concentration of 100 ⁇ M to multiple sets of 2B4 cultures and trypan blue dye exclusion was determined at various times after polypeptide addition.
  • Example 12 This example illustrates that the cell death induced by Tat-BH3 fusion polypeptides is not inhibited by BCL-2 and z- VAD-fmk.
  • Lys Lys Leu Ser Glu Cys Leu Arg Lys lie Gly Asp Glu Leu Asp Ser 1 5 10 15
  • MOLECULE TYPE protein
  • GAGAGCCCAT TCCCACCATT CTACCTGAGG CCAGGACGTC TGGGGTGTGG GGATTGGTGG 1260

Abstract

L'invention concerne de petits polypeptides et de petits peptides de 5 à 50 acides aminés présentant une activité agoniste de la mort cellulaire. Les polypeptides ont une longueur d'au moins 9 acides aminés et contiennent le domaine BH3 d'un membre de la famille BCL-2 pro-apoptotique. Les peptides contiennent de 5 à 8 acides aminés du domaine BH3. L'invention concerne également des méthodes favorisant l'apoptose avec ces polypeptides et peptides agonistes de la mort cellulaire, ainsi que les polynucléotides les codant.
PCT/US1998/019765 1997-09-26 1998-09-22 Agonistes de mort cellulaire WO1999016787A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU94028/98A AU9402898A (en) 1997-09-26 1998-09-22 Cell death agonists

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US6013397P 1997-09-26 1997-09-26
US60/060,133 1997-09-26
US94603997A 1997-10-07 1997-10-07
US08/946,039 1997-10-07

Publications (2)

Publication Number Publication Date
WO1999016787A1 true WO1999016787A1 (fr) 1999-04-08
WO1999016787A9 WO1999016787A9 (fr) 1999-06-24

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1998/019765 WO1999016787A1 (fr) 1997-09-26 1998-09-22 Agonistes de mort cellulaire

Country Status (2)

Country Link
AU (1) AU9402898A (fr)
WO (1) WO1999016787A1 (fr)

Cited By (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999050414A1 (fr) * 1998-03-31 1999-10-07 Thomas Jefferson University Genes blk et leurs utilisations dans l'apoptose
WO2000006187A2 (fr) * 1998-07-31 2000-02-10 Washington University Modulation d'apoptose
WO2001000670A1 (fr) * 1999-06-25 2001-01-04 Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. Peptides modifies bh3
US6221615B1 (en) 1995-05-12 2001-04-24 Apoptosis Technology, Inc. Peptides and compositions which modulate apoptosis
WO2002064766A2 (fr) * 2000-12-22 2002-08-22 Janssen Pharmaceutica N.V. Genes reagissant a bax, destines a l'identification des cibles de medicaments dans la levure et les champignons
US6737511B1 (en) 1999-08-16 2004-05-18 The United States Of America As Represented By The Department Of Health And Human Services Receptor-mediated uptake of an extracellular BCL-xL fusion protein inhibits apoptosis
WO2004089981A3 (fr) * 2003-04-02 2005-01-20 Univ Texas Effet antitumoral d'un mutant du bik
KR100685345B1 (ko) 2004-03-27 2007-02-22 학교법인조선대학교 세포사 유도 펩타이드
WO2007035494A2 (fr) * 2005-09-16 2007-03-29 The Regents Of The University Of California Induction de l'expression de puma permettant de reduire l'inflammation articulaire dans le traitement de l'arthrite
WO2008152405A2 (fr) * 2007-06-15 2008-12-18 The Queen's University Of Belfast Cible anti-cancer
US7723104B2 (en) 2004-04-02 2010-05-25 Board Of Regents, The University Of Texas System Cancer specific promoters
US8080517B2 (en) 2005-09-12 2011-12-20 Xigen Sa Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US8183339B1 (en) 1999-10-12 2012-05-22 Xigen S.A. Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US8236924B2 (en) 1999-10-12 2012-08-07 Xigen Sa Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US8748395B2 (en) 2005-09-12 2014-06-10 Xigen Inflammation Ltd. Cell-permeable peptide inhibitors of the JNK signal transduction pathway
CN104193826A (zh) * 2014-09-17 2014-12-10 山东大学齐鲁医院 一种融合多肽及其在制备抗肿瘤药物中的应用
US8981052B2 (en) 2010-06-21 2015-03-17 Xigen Inflammation Ltd. JNK inhibitor molecules
US9006185B2 (en) 2008-05-30 2015-04-14 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
WO2015092756A1 (fr) * 2013-12-22 2015-06-25 Uniwersytet Warszawski Protéine de fusion recombinante prostat et utilisations associées
US9150618B2 (en) 2010-10-14 2015-10-06 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of chronic or non-chronic inflammatory eye diseases
US9180159B2 (en) 2008-05-30 2015-11-10 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of chronic or non-chronic inflammatory digestive diseases
US10023615B2 (en) 2008-12-22 2018-07-17 Xigen Inflammation Ltd. Efficient transport into white blood cells
US10132797B2 (en) * 2016-12-19 2018-11-20 Tolero Pharmaceuticals, Inc. Profiling peptides and methods for sensitivity profiling
US10357488B2 (en) 2015-04-20 2019-07-23 Tolero Pharmaceuticals, Inc. Predicting response to alvocidib by mitochondrial profiling
US10413549B2 (en) 2012-11-21 2019-09-17 Eutropics Pharmaceuticals, Inc. Methods and compositions useful for treating diseases involving Bcl-2 family proteins with isoquinoline and quinoline derivatives
US10562925B2 (en) 2015-05-18 2020-02-18 Tolero Pharmaceuticals, Inc. Alvocidib prodrugs having increased bioavailability
US10568887B2 (en) 2015-08-03 2020-02-25 Tolero Pharmaceuticals, Inc. Combination therapies for treatment of cancer
US10596223B2 (en) 2011-12-21 2020-03-24 Xigen Inflammation Ltd. JNK inhibitor molecules for treatment of various diseases
US10624948B2 (en) 2013-06-26 2020-04-21 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
US10732182B2 (en) 2013-08-01 2020-08-04 Eutropics Pharmaceuticals, Inc. Method for predicting cancer sensitivity
US10765673B2 (en) 2012-06-20 2020-09-08 Eutropics Pharmaceuticals, Inc. Methods and compositions useful for treating diseases involving Bcl-2 family proteins with quinoline derivatives
US11034710B2 (en) 2018-12-04 2021-06-15 Sumitomo Dainippon Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US11279694B2 (en) 2016-11-18 2022-03-22 Sumitomo Dainippon Pharma Oncology, Inc. Alvocidib prodrugs and their use as protein kinase inhibitors
US11331364B2 (en) 2014-06-26 2022-05-17 Xigen Inflammation Ltd. Use for JNK inhibitor molecules for treatment of various diseases
US11497756B2 (en) 2017-09-12 2022-11-15 Sumitomo Pharma Oncology, Inc. Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib
US11519015B2 (en) 2013-10-30 2022-12-06 Entropics Pharmaceuticals, Inc. Methods for determining chemosensitivity and chemotoxicity
JP2023016769A (ja) * 2021-07-21 2023-02-02 チーリン ユニバーシティー 抗腫瘍ポリペプチドＢａｘ－ＢＨ３、蛍光高分子ナノミセルとその製造方法および使用
US11779628B2 (en) 2013-06-26 2023-10-10 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
US11793802B2 (en) 2019-03-20 2023-10-24 Sumitomo Pharma Oncology, Inc. Treatment of acute myeloid leukemia (AML) with venetoclax failure

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6774951B2 (ja) 2015-01-12 2020-11-04 ユートロピクス ファーマシューティカルズ， インコーポレイテッド 癌処置をガイドするためのコンテクストに依存する診断試験

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US5656725A (en) * 1995-05-12 1997-08-12 Apoptosis Technology, Inc. Peptides and compositions which modulate apoptosis

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* Cited by examiner, † Cited by third party
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US5656725A (en) * 1995-05-12 1997-08-12 Apoptosis Technology, Inc. Peptides and compositions which modulate apoptosis

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Title
BOYD J. M., ET AL.: "BIK, A NOVEL DEATH-INDUCING PROTEIN SHARES A DISTINCT SEQUENCE MOTIF WITH BCL-2 FAMILY PROTEINS AND INTERACTS WITH VIRAL AND CELLULAR SURVIVAL-PROMOTING PROTEINS.", ONCOGENE, NATURE PUBLISHING GROUP, GB, vol. 11., 1 January 1995 (1995-01-01), GB, pages 1921 - 1928., XP002915868, ISSN: 0950-9232 *
CHITTENDEN T, ET AL.: "A CONSERVED DOMAIN IN BAK, DISTINCT FROM BH1 AND BH2, MEDIATES CELLDEATH AND PROTEIN BINDING FUNCTIONS", EMBO JOURNAL., OXFORD UNIVERSITY PRESS, SURREY., GB, vol. 14, 1 January 1995 (1995-01-01), GB, pages 5589 - 5596, XP002915869, ISSN: 0261-4189 *
WANG K., ET AL.: "BID: A NOVEL BH3 DOMAIN-ONLY DEATH AGONIST.", GENES AND DEVELOPMENT., COLD SPRING HARBOR LABORATORY PRESS, PLAINVIEW, NY., US, vol. 10., 1 January 1996 (1996-01-01), US, pages 2859 - 2869., XP002915870, ISSN: 0890-9369 *

Cited By (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6221615B1 (en) 1995-05-12 2001-04-24 Apoptosis Technology, Inc. Peptides and compositions which modulate apoptosis
US7358088B2 (en) 1995-05-12 2008-04-15 Immunogen, Inc. Peptides and compositions which modulate apoptosis
US7097982B2 (en) 1995-05-12 2006-08-29 Immunogen, Inc. Peptides and compositions which modulate apoptosis
US6600024B1 (en) 1998-03-31 2003-07-29 Thomas Jefferson University Blk genes, gene products and uses thereof in apoptosis
WO1999050414A1 (fr) * 1998-03-31 1999-10-07 Thomas Jefferson University Genes blk et leurs utilisations dans l'apoptose
US6190912B1 (en) 1998-03-31 2001-02-20 Thomas Jefferson University Blk genes and uses thereof in apoptosis
WO2000006187A3 (fr) * 1998-07-31 2000-05-04 Univ Washington Modulation d'apoptose
WO2000006187A2 (fr) * 1998-07-31 2000-02-10 Washington University Modulation d'apoptose
WO2001000670A1 (fr) * 1999-06-25 2001-01-04 Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. Peptides modifies bh3
US6737511B1 (en) 1999-08-16 2004-05-18 The United States Of America As Represented By The Department Of Health And Human Services Receptor-mediated uptake of an extracellular BCL-xL fusion protein inhibits apoptosis
US8569447B2 (en) 1999-10-12 2013-10-29 Xigen Sa Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US8183339B1 (en) 1999-10-12 2012-05-22 Xigen S.A. Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US8278413B2 (en) 1999-10-12 2012-10-02 Xigen Sa Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US8236924B2 (en) 1999-10-12 2012-08-07 Xigen Sa Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US7101990B2 (en) 2000-12-22 2006-09-05 Janssen Pharmaceutica N.V. Bax-responsive genes for drug target identification in yeast and fungi
WO2002064766A3 (fr) * 2000-12-22 2003-06-26 Janssen Pharmaceutica Nv Genes reagissant a bax, destines a l'identification des cibles de medicaments dans la levure et les champignons
WO2002064766A2 (fr) * 2000-12-22 2002-08-22 Janssen Pharmaceutica N.V. Genes reagissant a bax, destines a l'identification des cibles de medicaments dans la levure et les champignons
WO2004089981A3 (fr) * 2003-04-02 2005-01-20 Univ Texas Effet antitumoral d'un mutant du bik
KR100685345B1 (ko) 2004-03-27 2007-02-22 학교법인조선대학교 세포사 유도 펩타이드
US7723104B2 (en) 2004-04-02 2010-05-25 Board Of Regents, The University Of Texas System Cancer specific promoters
US7816131B2 (en) 2004-04-02 2010-10-19 Board Of Regents, The University Of Texas System Cancer specific promoters
US8748395B2 (en) 2005-09-12 2014-06-10 Xigen Inflammation Ltd. Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US8080517B2 (en) 2005-09-12 2011-12-20 Xigen Sa Cell-permeable peptide inhibitors of the JNK signal transduction pathway
US9290538B2 (en) 2005-09-12 2016-03-22 Xigen Inflammation Ltd. Cell-permeable peptide inhibitors of the JNK signal transduction pathway
WO2007035494A3 (fr) * 2005-09-16 2007-10-18 Univ California Induction de l'expression de puma permettant de reduire l'inflammation articulaire dans le traitement de l'arthrite
WO2007035494A2 (fr) * 2005-09-16 2007-03-29 The Regents Of The University Of California Induction de l'expression de puma permettant de reduire l'inflammation articulaire dans le traitement de l'arthrite
WO2008152405A2 (fr) * 2007-06-15 2008-12-18 The Queen's University Of Belfast Cible anti-cancer
WO2008152405A3 (fr) * 2007-06-15 2009-04-09 Univ Belfast Cible anti-cancer
US9610330B2 (en) 2008-05-30 2017-04-04 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
US9006185B2 (en) 2008-05-30 2015-04-14 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
US9180159B2 (en) 2008-05-30 2015-11-10 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of chronic or non-chronic inflammatory digestive diseases
US10023615B2 (en) 2008-12-22 2018-07-17 Xigen Inflammation Ltd. Efficient transport into white blood cells
US8981052B2 (en) 2010-06-21 2015-03-17 Xigen Inflammation Ltd. JNK inhibitor molecules
US9624267B2 (en) 2010-06-21 2017-04-18 Xigen Inflammation Ltd. JNK inhibitor molecules
US9150618B2 (en) 2010-10-14 2015-10-06 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of chronic or non-chronic inflammatory eye diseases
US10596223B2 (en) 2011-12-21 2020-03-24 Xigen Inflammation Ltd. JNK inhibitor molecules for treatment of various diseases
US10765673B2 (en) 2012-06-20 2020-09-08 Eutropics Pharmaceuticals, Inc. Methods and compositions useful for treating diseases involving Bcl-2 family proteins with quinoline derivatives
US10413549B2 (en) 2012-11-21 2019-09-17 Eutropics Pharmaceuticals, Inc. Methods and compositions useful for treating diseases involving Bcl-2 family proteins with isoquinoline and quinoline derivatives
US10624948B2 (en) 2013-06-26 2020-04-21 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
US11779628B2 (en) 2013-06-26 2023-10-10 Xigen Inflammation Ltd. Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases
US10732182B2 (en) 2013-08-01 2020-08-04 Eutropics Pharmaceuticals, Inc. Method for predicting cancer sensitivity
US11519015B2 (en) 2013-10-30 2022-12-06 Entropics Pharmaceuticals, Inc. Methods for determining chemosensitivity and chemotoxicity
WO2015092756A1 (fr) * 2013-12-22 2015-06-25 Uniwersytet Warszawski Protéine de fusion recombinante prostat et utilisations associées
US11331364B2 (en) 2014-06-26 2022-05-17 Xigen Inflammation Ltd. Use for JNK inhibitor molecules for treatment of various diseases
CN104193826B (zh) * 2014-09-17 2018-02-23 山东大学齐鲁医院 一种融合多肽及其在制备抗肿瘤药物中的应用
CN104193826A (zh) * 2014-09-17 2014-12-10 山东大学齐鲁医院 一种融合多肽及其在制备抗肿瘤药物中的应用
US10624880B2 (en) 2015-04-20 2020-04-21 Tolero Pharmaceuticals, Inc. Predicting response to alvocidib by mitochondrial profiling
US10357488B2 (en) 2015-04-20 2019-07-23 Tolero Pharmaceuticals, Inc. Predicting response to alvocidib by mitochondrial profiling
US10562925B2 (en) 2015-05-18 2020-02-18 Tolero Pharmaceuticals, Inc. Alvocidib prodrugs having increased bioavailability
US10682356B2 (en) 2015-08-03 2020-06-16 Tolero Pharmaceuticals, Inc. Combination therapies for treatment of cancer
US10568887B2 (en) 2015-08-03 2020-02-25 Tolero Pharmaceuticals, Inc. Combination therapies for treatment of cancer
US10835537B2 (en) 2015-08-03 2020-11-17 Sumitomo Dainippon Pharma Oncology, Inc. Combination therapies for treatment of cancer
US11279694B2 (en) 2016-11-18 2022-03-22 Sumitomo Dainippon Pharma Oncology, Inc. Alvocidib prodrugs and their use as protein kinase inhibitors
US10422788B2 (en) 2016-12-19 2019-09-24 Tolero Pharmaceuticals, Inc. Profiling peptides and methods for sensitivity profiling
US10267787B2 (en) 2016-12-19 2019-04-23 Tolero Pharmaceuticals, Inc. Profiling peptides and methods for sensitivity profiling
US10132797B2 (en) * 2016-12-19 2018-11-20 Tolero Pharmaceuticals, Inc. Profiling peptides and methods for sensitivity profiling
US11497756B2 (en) 2017-09-12 2022-11-15 Sumitomo Pharma Oncology, Inc. Treatment regimen for cancers that are insensitive to BCL-2 inhibitors using the MCL-1 inhibitor alvocidib
US11034710B2 (en) 2018-12-04 2021-06-15 Sumitomo Dainippon Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US11530231B2 (en) 2018-12-04 2022-12-20 Sumitomo Pharma Oncology, Inc. CDK9 inhibitors and polymorphs thereof for use as agents for treatment of cancer
US11793802B2 (en) 2019-03-20 2023-10-24 Sumitomo Pharma Oncology, Inc. Treatment of acute myeloid leukemia (AML) with venetoclax failure
JP2023016769A (ja) * 2021-07-21 2023-02-02 チーリン ユニバーシティー 抗腫瘍ポリペプチドＢａｘ－ＢＨ３、蛍光高分子ナノミセルとその製造方法および使用

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AU9402898A (en) 1999-04-23

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