Details of the Drug

General Information of Drug (ID: DMIFCY2)

Drug Name
H3B-6545
Synonyms
JPFTZIJTXCHJNE-HMOQVRKWSA-N; SCHEMBL18261010; HY-112596; CS-0047714; (2e)-N,N-dimethyl-4-{[2-({5-[(1z)-4,4,4-trifluoro-1-(3-fluoro-1h-indazol-5-yl)-2-phenylbut-1-en-1-yl]pyridin-2-yl}oxy)ethyl]amino}but-2-enamide
Indication
Disease Entry ICD 11 Status REF
Breast cancer 2C60-2C65 Phase 1/2 [1]
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 3 Molecular Weight (mw) 567.6
Logarithm of the Partition Coefficient (xlogp) 6.3
Rotatable Bond Count (rotbonds) 11
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 9
Chemical Identifiers
Formula
C30H29F4N5O2
IUPAC Name
(E)-N,N-dimethyl-4-[2-[5-[(Z)-4,4,4-trifluoro-1-(3-fluoro-2H-indazol-5-yl)-2-phenylbut-1-enyl]pyridin-2-yl]oxyethylamino]but-2-enamide
Canonical SMILES
CN(C)C(=O)/C=C/CNCCOC1=NC=C(C=C1)/C(=C(/CC(F)(F)F)\\C2=CC=CC=C2)/C3=CC4=C(NN=C4C=C3)F
InChI
InChI=1S/C30H29F4N5O2/c1-39(2)27(40)9-6-14-35-15-16-41-26-13-11-22(19-36-26)28(21-10-12-25-23(17-21)29(31)38-37-25)24(18-30(32,33)34)20-7-4-3-5-8-20/h3-13,17,19,35H,14-16,18H2,1-2H3,(H,37,38)/b9-6+,28-24-
InChIKey
JPFTZIJTXCHJNE-HMOQVRKWSA-N
Cross-matching ID
PubChem CID
124091040
TTD ID
D0Z5VW
INTEDE ID
DR1799

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Estrogen receptor (ESR) TTZAYWL ESR1_HUMAN Antagonist [2]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [3]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Substrate [3]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [3]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [3]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [3]
Cytochrome P450 3A5 (CYP3A5) DEIBDNY CP3A5_HUMAN Substrate [3]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Substrate [3]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [3]
Cytochrome P450 2J2 (CYP2J2) DERSX5P CP2J2_HUMAN Substrate [3]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Breast cancer
ICD Disease Classification 2C60-2C65
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 9.78E-01 -3.38E-03 -5.71E-02
Cytochrome P450 2J2 (CYP2J2) DME CYP2J2 6.32E-01 -4.03E-02 -1.63E-01
Cytochrome P450 2B6 (CYP2B6) DME CYP2B6 3.97E-02 -1.72E-01 -9.29E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 9.96E-01 -7.53E-02 -5.68E-01
Cytochrome P450 3A5 (CYP3A5) DME CYP3A5 5.82E-01 -6.00E-02 -2.69E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 3.44E-01 -1.85E-01 -5.25E-01
Cytochrome P450 2D6 (CYP2D6) DME CYP2D6 7.95E-01 -7.47E-02 -2.45E-01
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 9.09E-01 -9.26E-02 -3.68E-01
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 9.85E-01 2.24E-02 7.33E-02
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 ClinicalTrials.gov (NCT03250676) Trial of H3B-6545, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 Negative Breast Cancer. U.S. National Institutes of Health.
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Nonclinical pharmacokinetics and in vitro metabolism of H3B-6545, a novel selective ERalpha covalent antagonist (SERCA). Cancer Chemother Pharmacol. 2019 Jan;83(1):151-160.