LY3200882 | CAS#1898283-02-7 | TGFβRI inhibitor

MedKoo Cat#: 206929 | Name: LY3200882

Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

LY3200882

CAS#1898283-02-7

Theoretical Analysis

MedKoo Cat#: 206929

Name: LY3200882

CAS#: 1898283-02-7

Chemical Formula: C24H29N5O3

Exact Mass: 435.2270

Molecular Weight: 435.53

Elemental Analysis: C, 66.19; H, 6.71; N, 16.08; O, 11.02

Price and Availability

Size	Price	Availability
5mg	USD 115.00	Ready to ship
10mg	USD 190.00	Ready to ship
25mg	USD 350.00	Ready to ship
50mg	USD 550.00	Ready to ship
100mg	USD 950.00	Ready to ship
200mg	USD 1,650.00	Ready to ship

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Related CAS #

No Data

Synonym

LY-3200882; LY 3200882; LY3200882.

IUPAC/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

InChi Key

PNPFMWIDAKQFPY-UHFFFAOYSA-N

InChi Code

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)

SMILES Code

CC(O)(C)C1=NC=CC(NC2=NC=CC(OC3=CN(C4CC4)N=C3C5CCOCC5)=C2)=C1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

The TGFb signaling pathway is often deregulated in tumors, and plays a key role in the regulation of cell growth, differentiation, apoptosis, motility, invasion, angiogenesis, and various immune responses. Mechanism of action studies reveal revealed that LY3200882 inhibits various pro-tumorigenic activities. LY3200882 potently inhibits TGFβ mediated SMAD phosphorylation in vitro in tumor and immune cells and in vivo in subcutaneous tumors in a dose dependent fashion. In preclinical tumor models, LY3200882 showed 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. Durable tumor regressions in the orthotopic 4T1-LP model were observed and rechallenge of congenic tumors resulted in complete rejection in all mice. In in vitro immune suppression assays, LY3200882 has shown the ability to rescue TGFβ1 suppressed or T regulatory cell suppressed naïve T cell activity and restore proliferation. Therefore, LY3200882 shows promising activity as an immune modulatory agent. In addition, LY3200882 has shown anti-metastatic activity in vitro in migration assays as well as in vivo in an experimental metastasis tumor model (intravenous EMT6-LM2 model of triple negative breast cancer). Finally, LY3200882 shows combinatorial anti-tumor benefits with checkpoint inhibition (anti-PD-L1) in the syngeneic CT26 model.

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#T8Z01C16

QC Data

View QC data: current batch, Lot#T8Z01C16

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

LY3200882 is an ATP-competitive TGF-β receptor type 1 (ALK5) inhibitor with an IC50 of 38.2 nM.

In vitro activity:

TBD

In vivo activity:

TBD

	Solvent	mg/mL	mM
Solubility
	DMSO	108.5	249.12

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 435.53 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

TBD

In vitro protocol:

TBD

In vivo protocol:

TBD

[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. https://aacrjournals.org/cancerres/article/77/13_Supplement/955/622127/Abstract-955-LY3200882-a-novel-highly-selective [2]. Xu G, Zhang Y, Wang H, Guo Z, Wang X, Li X, Chang S, Sun T, Yu Z, Xu T, Zhao L, Wang Y, Yu W. 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 Jul 15;198:112354. doi: 10.1016/j.ejmech.2020.112354. Epub 2020 Apr 29. PMID: 32387837.