Chemical Probes logo
MS6105 | MS6105 : Degrader (PROTAC) of LDHA, LDHB
RATINGS:
Cellular Use: (2 reviews)

In Model Organisms: (2 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
Vendors
Download

Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
LDHA
    • DC50:38 ± 0.5 nM
    • Dmax:93 ± 2.6%
    • GI50:16100 ± 5700 nM
    LDHB
      • DC50:74 ± 6.9 nM
      • Dmax:86 ± 7.7%
      Degrader (PROTAC)
      up to 1 uM

      Selectivity

      In Cell Selectivity Assessment
      Potency Assay Off-Target:
      Global proteomic profiling studies using a label-free quantitative mass spectrometry (MS) approach i ...
      Selectivity Assessment Description:
      The proteomics analysis showed that of the 52 down- and up-regulated proteins by MS6105 compared to ...

      Potency
      Cellular
      In Vitro

      LDHA

      Mode of Action: Degrader (PROTAC)

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.2c01505

      LDHB

      Mode of Action: Degrader (PROTAC)

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.2c01505

      In Vivo Validations

      Mouse
      Dose: 5 mg/Kg
      Route of delivery: Intraperitoneal
      Cmax: 1800 nM
      Tmax: 8 h

      DOI Reference: 10.1021/acs.jmedchem.2c01505

      Negative Control Compounds

      canSAR7083887
      Notes: Compound 33 was designed to prevent its binding to the VHL E3 ligase by benzylating the key hydroxy group of VHL-1, which is essential for binding VHL, tested at 0.1-3.0 uM it does not degrade LDH in PANC1 cells after 48h.
      canSAR7437565
      Notes: Compound 34 was designed to reduce binding to LDHA by replacing the key carboxylic acid group with the dimethyl amide group while keeping the linker and VHL binding moiety the same a MS6105, tested at 0.1-3.0 uM it does not degrade LDH in PANC1 cells after 48h.

      Chemical Information

      Molecular Formula C65H81N9O9S3
      SMILEs Cc1ncsc1-c1ccc(CNC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)CCCCCCCCCCCC(=O)NCCCCC#Cc2cccc(-c3nn(-c4nc(C(=O)O)cs4)c(CC4CC4)c3Cc3ccc(S(N)(=O)=O)cc3)c2)C(C)(C)C)cc1
      InChI InChI=1S/C65H81N9O9S3/c1-43-59(85-42-69-43)48-30-26-47(27-31-48)39-68-61(78)55-38-50(75)40-73(55)62(79)60(65(2,3)4)71-57(77)23-16-11-9-7-5-6-8-10-15-22-56(76)67-34-17-13-12-14-19-44-20-18-21-49(35-44)58-52(36-45-28-32-51(33-29-45)86(66,82)83)54(37-46-24-25-46)74(72-58)64-70-53(41-84-64)63(80)81/h18,20-21,26-33,35,41-42,46,50,55,60,75H,5-13,15-17,22-25,34,36-40H2,1-4H3,(H,67,76)(H,68,78)(H,71,77)(H,80,81)(H2,66,82,83)/t50-,55+,60-/m1/s1
      Molecular weight 1227.53 Da
      AlogP 10.054819999999998
      HBond acceptors 18
      HBond donors 7
      Atoms 167

      Expert Reviews

      by SERP
      (on 27 Jan 2025 )
      Cellular Use Rating
      In Model Organisms
      Sun et al. report 22, an LDH degrading PROTAC (VHL recruiting) based on the pyrazole scaffold discovered by NCATS (10.1021/acs.jmedchem.7b00941). 22 degrades LDHA and LDHB by western blot, while the VHL-binding-disrupted...
      by SERP+
      (on 6 Feb 2026 )
      Cellular Use Rating
      In Model Organisms
      Despite a reported DC50 of 38 nM and Dmax of 93% are dubious as further studies in the paper do not show significant degradation at 1uM or 3uM. There is some concern regarding the late degradation onset...
      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