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Daraxonrasib | Daraxonrasib : Inhibitor of KRAS, NRAS, HRAS and specific mutants thereof
RATINGS:
Cellular Use: (0 reviews)

In Model Organisms: (0 reviews)
Probe Summary
Selectivity
Potency
In Vivo
Control Compounds
Chemical Information
References
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Probe Summary

Targets Biochemical/Biophysical Potency Cellular Potency
KRAS (Mutant:WT, G12V, G12C, G12D)
  • IC50:92 nM
  • DC50:0.3 nM
  • EC50:1.6 nM
  • EC50:3.6 nM
  • EC50:1.3 nM
  • EC50:1.0 nM
  • EC50:3.2 nM
NRAS (Mutant:WT, NRAS Q61R)
  • IC50:about 90 nM
    HRAS
    • IC50:about 90 nM
      Inhibitor
      up to 1 uM

      Selectivity

      In Vitro Selectivity Assessment
      Potency Assay Off-Target:
      Daraxonrasib (RMC-6236) is not a potent inhibitor of human Ether-à-go-go-Related Gene (hERG), human ...

      Potency
      Cellular
      In Vitro

      KRAS (Mutant:WT, G12V, G12C, G12D)

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      NRAS (Mutant:WT, NRAS Q61R)

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      HRAS

      Mode of Action: Inhibitor

      Structure-Activity-Relationship data available? Yes

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      In Vivo Validations

      Mouse
      Dose: 1 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 2.2 h
      Systemic clearance: 0.5 L/h/Kg
      Volume of Distribution at Steady-State: 1.3 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Dose: 10 mg/Kg
      Route of delivery: Oral
      Plasma half life: 2.4 h
      Tmax: 1.7 h
      Bioavailability: 33%

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Rat
      Dose: 1 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 1.7 h
      Systemic clearance: 1.3 L/h/Kg
      Volume of Distribution at Steady-State: 1.3 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Dose: 60 mg/Kg
      Route of delivery: Oral
      Plasma half life: 2.8 h
      Tmax: 4.0 h
      Bioavailability: 27%

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Dog
      Dose: 1 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 6.1 h
      Systemic clearance: 0.4 L/h/Kg
      Volume of Distribution at Steady-State: 2.1 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Dose: 8 mg/Kg
      Route of delivery: Oral
      Plasma half life: 5.3 h
      Tmax: 0.7 h
      Bioavailability: 33%

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Monkey (Cynomolgus)
      Dose: 1 mg/Kg
      Route of delivery: Intravenous
      Plasma half life: 6.2 h
      Systemic clearance: 0.5 L/h/Kg
      Volume of Distribution at Steady-State: 2.9 L/Kg

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Dose: 2.5 mg/Kg
      Route of delivery: Oral
      Plasma half life: 4.6 h
      Tmax: 3.7 h
      Bioavailability: 24%

      DOI Reference: 10.1021/acs.jmedchem.4c02314

      Chemical Information

      Molecular Formula C44H58N8O5S
      SMILEs CCn1c(-c2cc(N3CCN(C)CC3)cnc2[C@H](C)OC)c2c3cc(ccc31)-c1csc(n1)C[C@H](NC(=O)[C@H]1C[C@@H]1C)C(=O)N1CCC[C@H](N1)C(=O)OCC(C)(C)C2
      InChI InChI=1S/C44H58N8O5S/c1-8-51-37-12-11-28-19-31(37)33(40(51)32-20-29(23-45-39(32)27(3)56-7)50-16-14-49(6)15-17-50)22-44(4,5)25-57-43(55)34-10-9-13-52(48-34)42(54)35(21-38-46-36(28)24-58-38)47-41(53)30-18-26(30)2/h11-12,19-20,23-24,26-27,30,34-35,48H,8-10,13-18,21-22,25H2,1-7H3,(H,47,53)/t26-,27-,30-,34-,35-/m0/s1
      Molecular weight 810.43 Da
      AlogP 5.610300000000005
      HBond acceptors 13
      HBond donors 2
      Atoms 116

      Expert Reviews

      No SERP comments found for Daraxonrasib

      Probe Daraxonrasib is in the process of SERP review.

      Please continue to check back for new reviews and commentary.