PIM447-VHL-01   Click here for help

GtoPdb Ligand ID: 13038

Compound class: Synthetic organic
Comment: PIM447-VHL-01 is a PIM1-selective PROTAC degrader [1]. The PIM-targeting warhead is the inhibitor PIM447, and this is linked to a VHL-binding ligand to engage the von Hippel-Lindau (VHL) Cullin 2-Ring ubiquitin ligase, and direct the PIM protein target for ubiquitin mediated degradation in the proteasome. PIM447-VHL-01 degrades PIM1 with no "hook-effect" at high doses.
2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 14
Hydrogen bond donors 5
Rotatable bonds 24
Topological polar surface area 219.32
Molecular weight 1023.22
XLogP 4.05
No. Lipinski's rules broken 3
SMILES / InChI / InChIKey
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Canonical SMILES C[C@H]1CC(C[C@H](C1)NC(=O)CCCCCCC(=O)N[C@H](C(=O)N2C[C@@H](C[C@H]2C(=O)N[C@@H](C)C3=CC=C(C=C3)C4=C(C)N=CS4)O)C(C)(C)C)C5=CC=NC=C5NC(=O)C6=CC=C(C(=N6)C7=C(C=CC=C7F)F)F
Isomeric SMILES C[C@H](NC(=O)[C@@H]1C[C@@H](O)CN1C(=O)[C@@H](NC(=O)CCCCCCC(=O)N[C@H]2C[C@@H](C)CC(C2)C3=CC=NC=C3NC(=O)C4=CC=C(F)C(=N4)C5=C(F)C=CC=C5F)C(C)(C)C)C6=CC=C(C=C6)C7=C(C)N=CS7
InChI InChI=1S/C55H65F3N8O6S/c1-31-24-36(39-22-23-59-28-44(39)64-52(70)43-21-20-42(58)49(63-43)48-40(56)12-11-13-41(48)57)26-37(25-31)62-46(68)14-9-7-8-10-15-47(69)65-51(55(4,5)6)54(72)66-29-38(67)27-45(66)53(71)61-32(2)34-16-18-35(19-17-34)50-33(3)60-30-73-50/h11-13,16-23,28,30-32,36-38,45,51,67H,7-10,14-15,24-27,29H2,1-6H3,(H,61,71)(H,62,68)(H,64,70)(H,65,69)/t31-,32-,36?,37-,38+,45-,51+/m0/s1
InChI Key XKKWVBFDKVNKHY-ROPADPDWSA-N
References
1. Torres-Ayuso P, Katerji M, Mehlich D, Lookingbill SA, Sabbasani VR, Liou H, Casillas AL, Chauhan SS, Serwa R, Rubin MR et al.. (2023)
PIM1 targeted degradation prevents the emergence of chemoresistance in prostate cancer.
Cell Chem Biol, Epub ahead of print. DOI: 10.1016/j.chembiol.2023.10.023