TNO155

TNO155 is an orally bioavailable allosteric inhibitor of Src homology region 2 domain-containing phosphatase 2 (SHP-2, IC50 = 0.011 µM). It is selective for SHP-2 over a panel of 52 kinases and phosphatases (IC50s = >10 µM for all). TNO155 decreases phosphorylation of ERK in, and inhibits proliferation of, KYSE-520 human esophageal cancer cells (IC50s = 0.011 and 0.1 µM, respectively). It acts synergistically with dabrafenib (Cay-16989) and trametinib (Cay-16292) to inhibit proliferation of B-RAFV600E-expressing HT-29, RKO, and MDST8 colorectal cancer cells. TNO155 (2.5, 10, and 20 mg/kg twice per day) reduces tumor growth in a KYSE-520 mouse xenograft model.Formal Name: (3S,4S)-8-[6-amino-5-[(2-amino-3-chloro-4-pyridinyl)thio]-2-pyrazinyl]-3-methyl-2-oxa-8-azaspiro[4.5]decan-4-amine. CAS Number: 1801765-04-7. Molecular Formula: C18H24ClN7OS. Formula Weight: 421.9. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMSO: soluble. lambdamax: 224, 269, 355 nm. SMILES: ClC1=C(N)N=CC=C1SC2=C(N)N=C(N3CCC4([C@H](N)[C@H](C)OC4)CC3)C=N2. InChi Code: InChI=1S/C18H24ClN7OS/c1-10-14(20)18(9-27-10)3-6-26(7-4-18)12-8-24-17(16(22)25-12)28-11-2-5-23-15(21)13(11)19/h2,5,8,10,14H,3-4,6-7,9,20H2,1H3,(H2,21,23)(H2,22,25)/t10-,14+/m0/s1. InChi Key: UCJZOKGUEJUNIO-IINYFYTJSA-N.