CA2705452C - Mapk/erk kinase inhibitors - Google Patents

Mapk/erk kinase inhibitors Download PDF

Info

Publication number
CA2705452C
CA2705452C CA2705452A CA2705452A CA2705452C CA 2705452 C CA2705452 C CA 2705452C CA 2705452 A CA2705452 A CA 2705452A CA 2705452 A CA2705452 A CA 2705452A CA 2705452 C CA2705452 C CA 2705452C
Authority
CA
Canada
Prior art keywords
alkyl
hetero
compound
fluoro
cycloalkyl
Prior art date
Legal status (The legal status 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 status listed.)
Expired - Fee Related
Application number
CA2705452A
Other languages
English (en)
French (fr)
Other versions
CA2705452A1 (en
Inventor
Mark E. Adams
Qing Dong
Stephen W. Kaldor
Toufike Kanouni
Nicholas Scorah
Michael B. Wallace
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Takeda Pharmaceutical Co Ltd
Original Assignee
Takeda Pharmaceutical Co Ltd
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 Takeda Pharmaceutical Co Ltd filed Critical Takeda Pharmaceutical Co Ltd
Publication of CA2705452A1 publication Critical patent/CA2705452A1/en
Application granted granted Critical
Publication of CA2705452C publication Critical patent/CA2705452C/en
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Diabetes (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Rheumatology (AREA)
  • Oncology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Communicable Diseases (AREA)
  • Obesity (AREA)
  • Transplantation (AREA)
  • Ophthalmology & Optometry (AREA)
  • Pain & Pain Management (AREA)
  • Vascular Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
CA2705452A 2007-11-12 2008-11-07 Mapk/erk kinase inhibitors Expired - Fee Related CA2705452C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US98727907P 2007-11-12 2007-11-12
US60/987,279 2007-11-12
PCT/US2008/082846 WO2009064675A1 (en) 2007-11-12 2008-11-07 Mapk/erk kinase inhibitors

Publications (2)

Publication Number Publication Date
CA2705452A1 CA2705452A1 (en) 2009-05-22
CA2705452C true CA2705452C (en) 2016-05-31

Family

ID=40340592

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2705452A Expired - Fee Related CA2705452C (en) 2007-11-12 2008-11-07 Mapk/erk kinase inhibitors

Country Status (10)

Country Link
US (1) US8022057B2 (enExample)
EP (1) EP2227469B9 (enExample)
JP (1) JP5453290B2 (enExample)
AR (1) AR069462A1 (enExample)
CA (1) CA2705452C (enExample)
CL (1) CL2008003366A1 (enExample)
ES (1) ES2456966T3 (enExample)
PE (1) PE20090998A1 (enExample)
TW (1) TW200934775A (enExample)
WO (1) WO2009064675A1 (enExample)

Families Citing this family (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7723477B2 (en) 2005-10-31 2010-05-25 Oncomed Pharmaceuticals, Inc. Compositions and methods for inhibiting Wnt-dependent solid tumor cell growth
MX2009004269A (es) 2006-10-23 2009-08-12 Takeda Pharmaceutical Inhibidores de cinasa mapk/erk.
JO2985B1 (ar) 2006-12-20 2016-09-05 Takeda Pharmaceuticals Co مثبطات كينازmapk/erk
CL2009000949A1 (es) * 2008-04-21 2010-12-24 Novartis Ag Compuestos derivados de 1,2,3,5-tetrahidro-indolizina, 6,7,8,9-tetrahidro-4h-quinolizina sustituidos, inhibidores de la actividad de cinasa de mek; su composicion farmaceutica; su uso para el tratamiento de enfermedades hiperproliferativas, tal como cancer e inflamaciones.
BRPI0919473A2 (pt) 2008-09-26 2017-08-29 Oncomed Pharm Inc Agentes de ligação frizzled e usos dos mesmos
JP2012524114A (ja) * 2009-04-21 2012-10-11 ノバルティス アーゲー Ｍｅｋ阻害剤としてのヘテロ環式化合物
MX2012005293A (es) * 2009-11-04 2012-06-19 Novartis Ag Derivados de sulfonamida heterociclicos utiles como inhibidores de mek.
WO2011067348A2 (en) 2009-12-03 2011-06-09 Novartis Ag Mek inhibitor salts and solvates thereof
CN101747300B (zh) * 2009-12-22 2012-11-07 上海大学 基于紫杉醇和氮芥的协同前药及其制备方法
TWI535445B (zh) 2010-01-12 2016-06-01 安可美德藥物股份有限公司 Ｗｎｔ拮抗劑及治療和篩選方法
CN102020651B (zh) 2010-11-02 2012-07-18 北京赛林泰医药技术有限公司 6-芳基氨基吡啶酮甲酰胺mek抑制剂
AU2012288865B2 (en) * 2011-07-27 2015-10-01 Glaxo Group Limited Bicyclic pyrimidone compounds
AR087405A1 (es) 2011-08-01 2014-03-19 Genentech Inc Metodos para tratar el cancer por el uso de antagonistas de union al eje pd-1 e inhibidores de mek
WO2013086260A2 (en) * 2011-12-09 2013-06-13 Oncomed Pharmaceuticals, Inc. Combination therapy for treatment of cancer
WO2013109142A1 (en) 2012-01-16 2013-07-25 Stichting Het Nederlands Kanker Instituut Combined pdk and mapk/erk pathway inhibition in neoplasia
SI2909182T1 (sl) 2012-10-19 2020-03-31 Array Biopharma Inc. Priprava inhibitorja MEK in formulacije, ki obsegajo inhibitor MEK
CN105073195A (zh) 2013-02-04 2015-11-18 昂科梅德制药有限公司 使用Wnt途径抑制剂进行治疗的方法及对该治疗的监测
JP2015003902A (ja) 2013-05-20 2015-01-08 杏林製薬株式会社 血管新生阻害剤
WO2014204263A1 (en) * 2013-06-20 2014-12-24 The Asan Foundation Substituted pyridinone compounds as mek inhibitors
WO2015041534A1 (en) 2013-09-20 2015-03-26 Stichting Het Nederlands Kanker Instituut P90rsk in combination with raf/erk/mek
US9629851B2 (en) 2013-09-20 2017-04-25 Stitching Het Nederlands Kanker Institut—Antoni Van Leeuwenhoek Ziekenhuis ROCK in combination with MAPK pathway
US20170027940A1 (en) 2014-04-10 2017-02-02 Stichting Het Nederlands Kanker Instituut Method for treating cancer
WO2015178770A1 (en) 2014-05-19 2015-11-26 Stichting Het Nederlands Kanker Instituut Compositions for cancer treatment
SG10202007111TA (en) 2014-07-15 2020-09-29 Genentech Inc Compositions for treating cancer using pd-1 axis binding antagonists and mek inhibitors
EP3355923B1 (en) 2015-10-01 2022-02-23 Stichting Het Nederlands Kanker Instituut- Antoni van Leeuwenhoek Ziekenhuis Histone deacetylase inhibitors for use in the treatment of drug resistant melanoma
WO2017099591A1 (en) 2015-12-07 2017-06-15 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Treatment of inhibitor resistant braf-mutant cancers
WO2017204626A1 (en) 2016-05-24 2017-11-30 Stichting Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Combination therapy - combined map2k4/map3k1 and mek/erk inhibition
WO2018218633A1 (en) 2017-06-02 2018-12-06 Beijing Percans Oncology Co. Ltd. Combination therapies for treating cancers
WO2019195959A1 (en) 2018-04-08 2019-10-17 Cothera Biosciences, Inc. Combination therapy for cancers with braf mutation
AU2019321289B2 (en) 2018-08-13 2025-01-23 Beijing Percans Oncology Co. Ltd. Biomarkers for cancer therapy
CN111662282B (zh) * 2019-03-07 2021-07-06 湖南化工研究院有限公司 氮杂环并吡啶类化合物及其中间体

Family Cites Families (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0670044B2 (ja) * 1987-11-20 1994-09-07 キッセイ薬品工業株式会社 ４ｈ―キノリジン―４―オン誘導体
AU616916B2 (en) 1987-11-20 1991-11-14 Kissei Pharmaceutical Co. Ltd. 4h-quinolizin-4-one compounds exhibiting therapeutic activities
WO1998037881A1 (en) 1997-02-28 1998-09-03 Warner Lambert Company Method of treating or preventing septic shock by administering a mek inhibitor
CA2349180A1 (en) 1999-01-13 2000-07-20 Stephen Douglas Barrett Anthranilic acid derivatives
US7235537B2 (en) 2002-03-13 2007-06-26 Array Biopharma, Inc. N3 alkylated benzimidazole derivatives as MEK inhibitors
PL401638A1 (pl) 2002-03-13 2013-05-27 Array Biopharma Inc. N3 alkilowane pochodne benzimidazolu jako inhibitory MEK
AR038972A1 (es) 2002-03-13 2005-02-02 Array Biopharma Inc Derivados de bencimidazol n3 alquilado como inhibidores de mek
WO2005000818A1 (en) 2003-06-27 2005-01-06 Warner-Lambert Company Llc 5-substituted-4-`(substituted phenyl)!amino!-2-pyridone deviatives for use as mek inhibitors
US20050049276A1 (en) * 2003-07-23 2005-03-03 Warner-Lambert Company, Llc Imidazopyridines and triazolopyridines
WO2005009975A2 (en) 2003-07-24 2005-02-03 Warner-Lambert Company Llc Benzimidazole derivatives as mek inhibitors
US7144907B2 (en) * 2003-09-03 2006-12-05 Array Biopharma Inc. Heterocyclic inhibitors of MEK and methods of use thereof
US7517994B2 (en) * 2003-11-19 2009-04-14 Array Biopharma Inc. Heterocyclic inhibitors of MEK and methods of use thereof
JP4768628B2 (ja) 2003-11-19 2011-09-07 アレイ バイオファーマ、インコーポレイテッド Ｍｅｋの二環系阻害剤及びその使用方法
WO2005121142A1 (en) 2004-06-11 2005-12-22 Japan Tobacco Inc. 5-amino-2,4,7-trioxo-3,4,7,8-tetrahydro-2h-pyrido’2,3-d! pyrimidine derivatives and related compounds for the treatment of cancer
JP2008520615A (ja) 2004-11-24 2008-06-19 ラボラトワール セローノ ソシエテ アノニム 過増殖性障害を処置するためのｍｅｋ阻害剤としての新規４−アリールアミノピリドン誘導体
AU2005311451A1 (en) 2004-12-01 2006-06-08 Merck Serono Sa [1,2,4]triazolo[4,3-a]pyridine derivatives for the treatment of hyperproliferative diseases
EP1967516B1 (en) 2005-05-18 2009-11-04 Array Biopharma, Inc. 4-(phenylamino)-6-oxo-1,6-dihydropyridazine-3-carboxamide derivatives as MEK inhibitors for the treatment of hyperproliferative diseases
MX2009004269A (es) * 2006-10-23 2009-08-12 Takeda Pharmaceutical Inhibidores de cinasa mapk/erk.
EP2089359A2 (en) * 2006-10-31 2009-08-19 Takeda Pharmaceutical Company Limited Mapk/erk kinase inhibitors
JO2985B1 (ar) * 2006-12-20 2016-09-05 Takeda Pharmaceuticals Co مثبطات كينازmapk/erk
CL2009000949A1 (es) * 2008-04-21 2010-12-24 Novartis Ag Compuestos derivados de 1,2,3,5-tetrahidro-indolizina, 6,7,8,9-tetrahidro-4h-quinolizina sustituidos, inhibidores de la actividad de cinasa de mek; su composicion farmaceutica; su uso para el tratamiento de enfermedades hiperproliferativas, tal como cancer e inflamaciones.
JP2012524114A (ja) 2009-04-21 2012-10-11 ノバルティス アーゲー Ｍｅｋ阻害剤としてのヘテロ環式化合物

Also Published As

Publication number Publication date
WO2009064675A1 (en) 2009-05-22
AR069462A1 (es) 2010-01-27
US20090124595A1 (en) 2009-05-14
EP2227469B1 (en) 2014-01-08
TW200934775A (en) 2009-08-16
JP5453290B2 (ja) 2014-03-26
EP2227469A1 (en) 2010-09-15
EP2227469B9 (en) 2014-09-10
US8022057B2 (en) 2011-09-20
ES2456966T3 (es) 2014-04-24
CL2008003366A1 (es) 2009-05-29
PE20090998A1 (es) 2009-08-12
JP2011503099A (ja) 2011-01-27
CA2705452A1 (en) 2009-05-22

Similar Documents

Publication Publication Date Title
CA2705452C (en) Mapk/erk kinase inhibitors
CA2673647C (en) Mapk/erk kinase inhibitors
EP2150544B1 (en) Mapk/erk kinase inhibitors
EP2113500A1 (en) MAPK/ERK kinase inhibitors
US7943626B2 (en) Substituted 1,3-dialkyl-2,4-dioxo-6-(pyridylamino)-1,2,3,4-tetrahydropyrimidine-5-hydroxamic acid inhibitors of MAPK/ERK kinase
US20090246198A1 (en) Mapk/erk kinase inhibitors and methods of use thereof
US20080312307A1 (en) Mapk/erk kinase inhibitors

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20131106

MKLA Lapsed

Effective date: 20171107