| Identification | Back Directory | [Name]
SHP099 | [CAS]
1801747-42-1 | [Synonyms]
SHP099
SHP-099 (free base)
6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine
6-(4-Amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-2-pyrazinamine
2-Pyrazinamine, 6-(4-amino-4-methyl-1-piperidinyl)-3-(2,3-dichlorophenyl)-
6-(4-Azanyl-4-Methyl-Piperidin-1-Yl)-3-[2,3-Bis(Chloranyl)phenyl]pyrazin-2-Amine | [Molecular Formula]
C16H19Cl2N5 | [MDL Number]
MFCD29059453 | [MOL File]
1801747-42-1.mol | [Molecular Weight]
352.26 |
| Chemical Properties | Back Directory | [Boiling point ]
530.4±50.0 °C(Predicted) | [density ]
1.326±0.06 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
Water:1.0(Max Conc. mg/mL);2.84(Max Conc. mM)
DMSO:21.0(Max Conc. mg/mL);34.07(Max Conc. mM) | [form ]
A crystalline solid | [pka]
9.05±0.20(Predicted) | [color ]
Light yellow to yellow | [InChI]
InChI=1S/C16H19Cl2N5/c1-16(20)5-7-23(8-6-16)12-9-21-14(15(19)22-12)10-3-2-4-11(17)13(10)18/h2-4,9H,5-8,20H2,1H3,(H2,19,22) | [InChIKey]
YGUFCDOEKKVKJK-UHFFFAOYSA-N | [SMILES]
C1(N)=NC(N2CCC(N)(C)CC2)=CN=C1C1=CC=CC(Cl)=C1Cl |
| Hazard Information | Back Directory | [Uses]
SHP099 is an allosteric SHP2 inhibitor, with IC50s of 0.690, 1.241, 0.416, 1.968, 2.896 μM for SHP2, SHP2D61Y, SHP2E69K, SHP2A72V, SHP2E76K. SHP099 inhibits cancer cell growth, such as MV4-11 and TF-1 cell (IC50: 0.32 and 1.73 μM). SHP099 inhibits RAS-ERK signaling and inhibits tumor growth[1][2]. | [in vivo]
After a single dose of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg[1]. | [References]
[1] Chen YN, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52. DOI:10.1038/nature18621
[2] Sun X, et al. Selective inhibition of leukemia-associated SHP2E69K mutant by the allosteric SHP2 inhibitor SHP099. Leukemia. 2018 May;32(5):1246-1249. DOI:10.1038/s41375-018-0020-5 |
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