Siremadlin

Siremadlin is an inhibitor of the protein-protein interaction between the E3 ubiquitin ligase MDM2 and p53 (IC50 = 0.21 nM). It selectively inhibits the MDM2-p53 protein-protein interaction over MDM4-p53, YAP1-TEAD4, PCSK9-LDLR, and Bcl-2-Bak interactions in time-resolved FRET (TR-FRET) assays (IC50s = 3.3, >150, >50, and >50 µM, respectively). Siremadlin inhibits the growth of SJSA-1 osteosarcoma cells (GI50 = 38 nM). It also induces apoptosis in SJSA-1 cells when used at a concentration of 100 nM. In vivo, siremadlin (27 mg/kg) induces tumor regression and prevents tumor regrowth in an SJSA-1 rat xenograft model and an HSAX2655 patient-derived xenograft (PDX) rat liposarcoma model.Formal Name: (6S)-5-(5-chloro-1,2-dihydro-1-methyl-2-oxo-3-pyridinyl)-6-(4-chlorophenyl)-2-(2,4-dimethoxy-5-pyrimidinyl)-5,6-dihydro-1-(1-methylethyl)-pyrrolo[3,4-d]imidazol-4(1H)-one. CAS Number: 1448867-41-1. Synonyms: HDM201, NVP-HDM201. Molecular Formula: C26H24Cl2N6O4. Formula Weight: 555.4. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMF: 20 mg/ml, DMSO: 10 mg/ml, Ethanol: 15 mg/ml. lambdamax: 223, 336 nm. SMILES: ClC1=CC=C([C@@H]2N(C(C3=C2N(C(C)C)C(C4=CN=C(N=C4OC)OC)=N3)=O)C5=CC(Cl)=CN(C5=O)C)C=C1. InChi Code: InChI=1S/C26H24Cl2N6O4/c1-13(2)33-21-19(30-22(33)17-11-29-26(38-5)31-23(17)37-4)25(36)34(18-10-16(28)12-32(3)24(18)35)20(21)14-6-8-15(27)9-7-14/h6-13,20H,1-5H3/t20-/m0/s1. InChi Key: AGBSXNCBIWWLHD-FQEVSTJZSA-N.