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S63845 | S63845 : BH3 mimetic inhibitor of MCL1
RATINGS:
Cellular Use: (4 reviews)

In Model Organisms: (4 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
MCL1
  • KD:MCL1: 0.19 nM
  • IC50:< 10 nM
BH3 mimetic
up to 1 uM

Selectivity

In Vitro Selectivity Assessment

Potency: Ki - BCL2 >10,000 nM, BCLXL >10,000 nM

Potency Assay Off-Target:
FP assay
Selectivity Assessment Description:
<strong>Outside Target Family:</strong>&nbsp;S63845 had little activity in BCL2 or BCLXL-dependen ...
In Cell Selectivity Assessment
Potency Assay Off-Target:
S63845 had little activity in BCL2 or BCLXL-dependent H146 cells in apoptosis assays.

Potency
Cellular
In Vitro

MCL1

Mode of Action: BH3 mimetic

Structure-Activity-Relationship data available? No

In Vivo Validations

SCID and C57BL/6 mice
Dose: 25 mg/kg, Reviewer suggested dose: 6.25-25 mg/Kg IV
Route of delivery: Intravenous
Organ of interest (O): Xenografts, various
Target engagement assay: In several xengraft models hematological and solid tumors, S63845 had anti-tumor activity. At the maximum dose (60 mg/kg), S63845 led to marked reduction in erythocytes.

Reference: --

Orthogonal Probes def

A-1210477
AMG-176

Chemical Information

Molecular Formula C39H37ClF4N6O6S
SMILEs Cc1c(-c2c(-c3ccc(F)o3)sc3ncnc(O[C@H](Cc4ccccc4OCc4ccnn4CC(F)(F)F)C(=O)O)c23)ccc(OCCN2CCN(C)CC2)c1Cl
InChI InChI=1S/C39H37ClF4N6O6S/c1-23-26(7-8-28(34(23)40)53-18-17-49-15-13-48(2)14-16-49)32-33-36(45-22-46-37(33)57-35(32)29-9-10-31(41)55-29)56-30(38(51)52)19-24-5-3-4-6-27(24)54-20-25-11-12-47-50(25)21-39(42,43)44/h3-12,22,30H,13-21H2,1-2H3,(H,51,52)/t30-/m1/s1
Molecular weight 828.21 Da
AlogP 7.757920000000009
HBond acceptors 12
HBond donors 1
Atoms 94

References

Publications

    Cross References

    canSARChEMBLBindingDBPDBPubMedPubMedPubMed

    Vendors

    Note: This is not an exhaustive list and does not indicate endorsement by the portal.

    Expert Reviews

    by SERP
    (on 28 Apr 2017 )
    Cellular Use Rating
    In Model Organisms
    S63845 is an excellent inhibitor with good potency and selectivity over other BCL2 family members (namely BCL2 and BCL-xL). It is active within mouse in vivo models at reasonable doses with no observable...
    by SERP
    (on 17 May 2017 )
    Cellular Use Rating
    In Model Organisms
    S63845 is a potent and selective MCL-1 inhibitor that is appropriate to use in cellular and in vivo studies. Based on its pharmacokinetic properties, S63845 cannot be dosed orally but requires intravenous...
    by SERP
    (on 24 May 2021 )
    Cellular Use Rating
    In Model Organisms
    S63845 is a tool compound that was published in 2016 and apparently originated from an optimization program at Servier/WEHI leading to the clinical stage Mcl1 inhibitor S64315. Currently, the published...
    by SERP
    (on 18 Jun 2021 )
    Cellular Use Rating
    In Model Organisms
    This probe is also very potent with many other cancer cell line tested, e.g. multiple myeloma derived and lymphoma cell line, as well as some patient, derived samples; No PK/PD relationship showed in...
    Note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars. Read more about our evaluation criteria