LY3200882

LY3200882 is an orally active TGFbeta inhibitor. LY3200882 targets transforming growth factor-beta (TGFb), with potential antineoplastic activity. Upon administration, LY3200882 specifically targets and binds to TGFb, which prevents both the binding of TGFb to its receptor TGFbR and TGFb-mediated signal transduction. This may lead to a reduction in TGFb-dependent proliferation of cancer cells.

Product information

CAS Number: 1898283-02-7

Molecular Weight: 435.52

Formula: C24H29N5O3

Chemical Name: 2-(4-((4-((1-cyclopropyl-3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-4-yl)oxy)pyridin-2-yl)amino)pyridin-2-yl)propan-2-ol

Smiles: CC(C)(O)C1=CC(=CC=N1)NC1=CC(=CC=N1)OC1=CN(N=C1C1CCOCC1)C1CC1

InChiKey: PNPFMWIDAKQFPY-UHFFFAOYSA-N

InChi: InChI=1S/C24H29N5O3/c1-24(2,30)21-13-17(5-9-25-21)27-22-14-19(6-10-26-22)32-20-15-29(18-3-4-18)28-23(20)16-7-11-31-12-8-16/h5-6,9-10,13-16,18,30H,3-4,7-8,11-12H2,1-2H3,(H,25,26,27)

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

In Vitro:

LY3200882 potently inhibits TGFβ mediated SMAD phosphorylation in vitro in tumor and immune cells in a dose dependent fashion. LY3200882 shows potent anti-tumor activity in the orthotopic 4T1-LP model of triple negative breast cancer and this activity correlated with enhanced tumor infiltrating lymphocytes in the tumor microenvironment[1]. In in vitro immune suppression assays, LY3200882 has shown the ability to rescue TGFβ1 suppressed or T regulatory cell suppressed naive T cell activity and restore proliferation. LY3200882 inhibits NIH3T3 cell viability with an IC50 of 82.9 nM.

In Vivo:

LY3200882 (60 mg/kg; oral gavage; twice a day; for 21 days; BALB/C female mice) treatment significantly delays tumor growth in CT26 model. LY3200882 potently inhibits TGFβ mediated SMAD phosphorylation in vivo in subcutaneous tumors in a dose dependent fashion. LY3200882 has shown anti-metastatic activity in vivo in an experimental metastasis tumor model (intravenous EMT6-LM2 model of triple negative breast cancer).

References:

1. Huaxing Pei, et al. Abstract 955: LY3200882, a novel, highly selective TGFβRI small molecule inhibitor. AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 955.
2. Xu G, et al. Synthesis and biological evaluation of 4-(pyridin-4-oxy)-3-(3,3-difluorocyclobutyl)-pyrazole derivatives as novel potent transforming growth factor-β type 1 receptor inhibitors. Eur J Med Chem. 2020 Apr 29;198:112354.

Products are for research use only. Not for human use.