For research use only. Not for therapeutic Use.
SIM1 is a potent von Hippel-Lindau (VHL)-based trivalent PROTAC capable of degradation for all BET family members, with preference for BRD2 degradation (IC50=1.1 nM; Kd=186 nM). SIM1 shows sustained anti-cancer activity[1].
SIM1 (1 nM; 30 hours; MV4-11 cells) results in measurable cellular death after 6 hours[1].?
SIM1 (1 μM; 4 hours; HEK293 cells) degrades BET proteins[1].?
SIM1 induces conformational changes upon binding to the BET protein to simultaneously engage with high avidity both its bromodomains in a cis intramolecular fashion. SIM1 engages BD1 and BD2 intramolecularly and forms a 1:1:1 ternary complex with VHL and BRD4[1].
| CAS Number | 2719051-84-8 |
| Synonyms | (2S,4R)-1-[(2S)-2-[[2-[3-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]-2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxymethyl]-2-methylpropoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide |
| Molecular Formula | C79H98Cl2N14O13S3 |
| Purity | ≥95% |
| InChI | InChI=1S/C79H98Cl2N14O13S3/c1-46-49(4)110-76-66(46)68(54-16-20-57(80)21-17-54)86-60(72-91-89-51(6)94(72)76)37-63(97)82-24-26-102-28-30-104-32-34-106-42-79(11,44-108-41-65(99)88-71(78(8,9)10)75(101)93-40-59(96)36-62(93)74(100)84-39-53-12-14-56(15-13-53)70-48(3)85-45-109-70)43-107-35-33-105-31-29-103-27-25-83-64(98)38-61-73-92-90-52(7)95(73)77-67(47(2)50(5)111-77)69(87-61)55-18-22-58(81)23-19-55/h12-23,45,59-62,71,96H,24-44H2,1-11H3,(H,82,97)(H,83,98)(H,84,100)(H,88,99)/t59-,60+,61+,62+,71-/m1/s1 |
| InChIKey | RARNTROXRCXFHV-CMRSQZKGSA-N |
| SMILES | CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)NCCOCCOCCOCC(C)(COCCOCCOCCNC(=O)CC4C5=NN=C(N5C6=C(C(=C(S6)C)C)C(=N4)C7=CC=C(C=C7)Cl)C)COCC(=O)NC(C(=O)N8CC(CC8C(=O)NCC9=CC=C(C=C9)C1=C(N=CS1)C)O)C(C)(C)C)C1=CC=C(C=C1)Cl)C |
| Reference | [1]. Satomi Imaide, et al. Trivalent PROTACs enhance protein degradation through cooperativity and avidity. Biological and Medicinal Chemistry. |
| Chemistry Calculators | Dilution Calculator In vivo Formulation Calculator Molarity Calculator Molecular Weight Calculator Reconstitution Calculator |
