LY2157299, a specific and potent TGF-β receptor (TβR) inhibitor that competitively binds to the active site of its kinase domain1, inhibiting TGF-β-mediated SMAD2 phosphorylation/activation and down streaming signaling.
LY2157299 inhibited hematopoetic suppression in primary hematopoietic stem cells, such that it improved anemia in a TGF-β overexpressing transgenic mouse model, and stimulated hematopoiesis from primary MDS bone marrow specimens2. Daily oral administration of LY2157299 in patients with advanced/metastatic cancer was tolerated well with an expected pharmacokinetic profile3,4.
Technical information:
| Chemical Formula: | C22H19N5O | |
| CAS #: | 700874-72-2, 912477-03-3 | |
| Molecular Weight: | 369.42 | |
| Purity: | >98% | |
| Appearance: | Off white solid | |
| Chemical Name: | 4-[2-(6-Methyl-pyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]-quinoline-6-carboxylic acid amide | |
| Solubility: | Up to 50 mM in DMSO |
Shipping Condition: The product is shipped in a glass vial at ambient temperature.
Storage: For longer shelf life, store solid powder at 4oC desiccated, or store DMSO solution at -20oC.
Reference:
| 1. | Yingling, J. et al. Targeting the TGF-ß RI kinase with LY2157299: A PK/PD-driven drug discovery and clinical development program. Proc Amer Assoc Cancer Res, 46, SY13-2, (2005). |
| 2. | Zhou L., et al. Reduced SMAD7 leads to overactivation of TGF-beta signaling in MDS that can be reversed by a specific inhibitor of TGF-beta receptor I kinase. Cancer Res. 71(3):955-63. (2011). |
| 3. | Bueno, L.,et al. Semi-mechanistic modelling of the tumour growth inhibitory effects of LY2157299, a new type I receptor TGF-b kinase antagonist, in mice. Eur J Cancer., 44(1):142-150, (2008). |
| 4. | E. Calvo-Aller et al. First human dose escalation study in patients with metastatic malignancies to determine safety and pharmacokinetics of LY2157299, a small molecule inhibitor of the transforming growth factor-beta receptor I kinase. J Clin Oncol 26: (May 20 suppl; abstr 14554), (2008) |
Other Information:
Product Specification (pdf)
MSDS (pdf)
