Details of the Drug

General Information of Drug (ID: DM7CNTG)

Drug Name

AMG 397

Synonyms

UNII-BO0V7196L2; BO0V7196L2; Murizatoclax; Murizatoclax [USAN]; SCHEMBL21040009; WHO 11281; (13S,31R,32R,4R,5E,8S,9R)-6'-Chloro-4-methoxy-8,9-dimethyl-4-(((9aR)-octahydro-2H-pyrido(1,2-a)pyrazin-2-yl)methyl)-3',4'-dihydro-12H,14H,2'Hspiro(10lambda6-thia-11-aza-1(5,7)-(1,5)benzoxazepina-3(1,2)-cyclobutanacyclododecaphan-5-ene-13,1'-naphthalene)-10,10,12-trione; 2245848-05-7; Spiro(5,7-etheno-1H,11H-cyclobut(i)(1,4)oxazepino(3,4-f)(1,2,7)thiadiazacyclohexadecine-2(3H),1'(2'H)-naphthalen)-8(9H)-one, 6'-chloro-3',4',12,13,16,16a,17,18,18a,19-decahydro-16-methoxy-11,12-dimethyl-16-(((9aR)-octahydro-2H-pyrido(1,2-a)pyrazin-2-yl)methyl)-, 10,10-dioxide, (1'S,11R,12S,14E,16R,16aR,18aR)-

Indication

Disease Entry	ICD 11	Status	REF
Refractory hematologic malignancy	2A85.5	Phase 1	[1]

Drug Type

Small molecular drug

Structure

3D MOL is unavailable

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

765.4

Topological Polar Surface Area (xlogp)

7.3

Rotatable Bond Count (rotbonds)

3

Hydrogen Bond Donor Count (hbonddonor)

1

Hydrogen Bond Acceptor Count (hbondacc)

8

Chemical Identifiers

Formula: C42H57ClN4O5S
IUPAC Name: (3'R,4S,6'R,7'R,8'E,11'S,12'R)-7'-[[(9aR)-1,3,4,6,7,8,9,9a-octahydropyrido[1,2-a]pyrazin-2-yl]methyl]-7-chloro-7'-methoxy-11',12'-dimethyl-13',13'-dioxospiro[2,3-dihydro-1H-naphthalene-4,22'-20-oxa-13lambda6-thia-1,14-diazatetracyclo[14.7.2.03,6.019,24]pentacosa-8,16(25),17,19(24)-tetraene]-15'-one
Canonical SMILES: C[C@H]1C/C=C/[C@@]([C@@H]2CC[C@H]2CN3C[C@@]4(CCCC5=C4C=CC(=C5)Cl)COC6=C3C=C(C=C6)C(=O)NS(=O)(=O)[C@@H]1C)(CN7CCN8CCCC[C@@H]8C7)OC
InChI: InChI=1S/C42H57ClN4O5S/c1-29-8-6-18-42(51-3,27-45-20-21-46-19-5-4-10-35(46)25-45)37-14-11-33(37)24-47-26-41(17-7-9-31-22-34(43)13-15-36(31)41)28-52-39-16-12-32(23-38(39)47)40(48)44-53(49,50)30(29)2/h6,12-13,15-16,18,22-23,29-30,33,35,37H,4-5,7-11,14,17,19-21,24-28H2,1-3H3,(H,44,48)/b18-6+/t29-,30+,33-,35+,37+,41-,42-/m0/s1
InChIKey: BJTFTQIBRVBSBH-VCQPVEJUSA-N

Cross-matching ID

PubChem CID: 138669688
CAS Number: 2245848-05-7
TTD ID: DBI81F

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	TTL53M6	MCL1_HUMAN	Inhibitor	[2]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Molecular Expression Atlas of This Drug

The Studied Disease

Refractory hematologic malignancy

ICD Disease Classification

2A85.5

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1)	DTT	MCL1	1.06E-04	1.29	2.97

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	ClinicalTrials.gov (NCT03465540) Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies. U.S. National Institutes of Health.
2	Clinical pipeline report, company report or official report of Amgen.
3	Phase II study of obatoclax mesylate (GX15-070), a small-molecule BCL-2 family antagonist, for patients with myelofibrosis. Clin Lymphoma Myeloma Leuk. 2010 Aug;10(4):285-9.
4	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
5	Clinical pipeline report, company report or official report of Prelude Therapeutics.
6	Clinical pipeline report, company report or official report of AbbVie.
7	MCL1 inhibitors S63845/MIK665 plus Navitoclax synergistically kill difficult-to-treat melanoma cells. Cell Death Dis. 2020 Jun 8;11(6):443.
8	Mcl-1 inhibitors: a patent review.Expert Opin Ther Pat. 2017 Feb;27(2):163-178.