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Discovery of MDV6058 (PF-06952229), a selective and potent TGFßR1 inhibitor: Design, synthesis and optimization.
Pujala, Brahmam; Ramachandran, Sreekanth A; Sonawane, Mukesh; Kamble, Maruti M; Panpatil, Dayanand; Adhikari, Swati; Soni, Sanjeev; Subbareddy, Venkata; Shinde, Bharat U; Nayak, Anjan K; Bansal, Chandni; Gupta, Ashu; Mukherjee, Kakoli; Agarwal, Anil K; Guerrero, Javier; Herrera, Francisco J; Bernales, Sebastian; Guha, Mausumee; Chakravarty, Sarvajit; Pham, Son M; Rai, Roopa.
Afiliação
  • Pujala B; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Ramachandran SA; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Sonawane M; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Kamble MM; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Panpatil D; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Adhikari S; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Soni S; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Subbareddy V; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Shinde BU; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Nayak AK; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Bansal C; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Gupta A; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Mukherjee K; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Agarwal AK; Integral BioSciences Pvt. Ltd., C-64, Hosiery Complex Phase II Extension, Noida, Uttar Pradesh 201306, India.
  • Guerrero J; Fundación Ciencia & Vida, Avenida Zañartu 1482, Ñuñoa, Santiago, 778027, Chile.
  • Herrera FJ; Medivation, Inc., 525 Market Street, 36(th) Floor, San Francisco, CA 94105, USA.
  • Bernales S; Medivation, Inc., 525 Market Street, 36(th) Floor, San Francisco, CA 94105, USA.
  • Guha M; Medivation, Inc., 525 Market Street, 36(th) Floor, San Francisco, CA 94105, USA; Pfizer Inc., Pfizer World Wide Research & Development, Building CB-4, 10777 Science Center Dr. La Jolla, CA 92121-1111, USA.
  • Chakravarty S; Medivation, Inc., 525 Market Street, 36(th) Floor, San Francisco, CA 94105, USA.
  • Pham SM; Medivation, Inc., 525 Market Street, 36(th) Floor, San Francisco, CA 94105, USA.
  • Rai R; Medivation, Inc., 525 Market Street, 36(th) Floor, San Francisco, CA 94105, USA. Electronic address: roopa.rai@hotmail.com.
Bioorg Med Chem Lett ; 75: 128979, 2022 11 01.
Article em En | MEDLINE | ID: mdl-36089110
ABSTRACT
Compound 1 is a potent TGF-ß receptor type-1 (TGFßR1 or ALK5) inhibitor but is metabolically unstable. A solvent-exposed part of this molecule was used to analogue and modulate cell activity, liver microsome stability and mouse pharmacokinetics. The evolution of SAR that led to the selection of 2 (MDV6058 / PF-06952229) as a preclinical lead compound is described.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Fatores de Crescimento Transformadores beta Limite: Animals Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Índia
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Receptores de Fatores de Crescimento Transformadores beta Limite: Animals Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Índia