Details of the Drug

General Information of Drug (ID: DMBR8NF)

Drug Name

MLN2480

Synonyms

VWMJHAFYPMOMGF-ZCFIWIBFSA-N; 1096708-71-2; MLN 2480; BIIB-024; Tak-580; MLN-2480; BIIB024; UNII-ZN90E4027M; BIIB 024; 4-Pyrimidinecarboxamide, 6-amino-5-chloro-N-[(1R)-1-[5-[[[5-chloro-4-(trifluoromethyl)-2-pyridinyl]amino]carbonyl]-2-thiazolyl]ethyl]-; ZN90E4027M; (r)-2-(1-(6-amino-5-chloropyrimidine-4-carboxamido)ethyl)-n-(5-chloro-4-(trifluoromethyl)pyridin-2-yl)thiazole-5-carboxamide; 4-Pyrimidinecarboxamide, 6-amino-5-chloro-N-((1R)-1-(5-(((5-chloro-4-(trifluoromethyl)-2-pyridinyl)amino)carbonyl)-2-thiazolyl)ethyl]-; AMG 2112819

Indication

Disease Entry	ICD 11	Status	REF
Solid tumour/cancer	2A00-2F9Z	Phase 2	[1]
Melanoma	2C30	Phase 1	[2]

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 2

Molecular Weight (mw)

506.3

Topological Polar Surface Area (xlogp)

3

Rotatable Bond Count (rotbonds)

5

Hydrogen Bond Donor Count (hbonddonor)

3

Hydrogen Bond Acceptor Count (hbondacc)

11

Chemical Identifiers

Formula: C17H12Cl2F3N7O2S
IUPAC Name: 2-[(1R)-1-[(6-amino-5-chloropyrimidine-4-carbonyl)amino]ethyl]-N-[5-chloro-4-(trifluoromethyl)pyridin-2-yl]-1,3-thiazole-5-carboxamide
Canonical SMILES: C[C@H](C1=NC=C(S1)C(=O)NC2=NC=C(C(=C2)C(F)(F)F)Cl)NC(=O)C3=C(C(=NC=N3)N)Cl
InChI: InChI=1S/C17H12Cl2F3N7O2S/c1-6(28-15(31)12-11(19)13(23)27-5-26-12)16-25-4-9(32-16)14(30)29-10-2-7(17(20,21)22)8(18)3-24-10/h2-6H,1H3,(H,28,31)(H2,23,26,27)(H,24,29,30)/t6-/m1/s1
InChIKey: VWMJHAFYPMOMGF-ZCFIWIBFSA-N

Cross-matching ID

PubChem CID: 25161177
CAS Number: 1096708-71-2
TTD ID: D07IEU

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
B-Raf messenger RNA (BRAF mRNA)	TT0EOB8	BRAF_HUMAN	Inhibitor	[3]
Raf messenger RNA (Raf mRNA)	TTAN5W2	RAF1_HUMAN	Inhibitor	[4], [5]
Serine/threonine-protein kinase Raf (RAF)	TTQ9K3Y	ARAF_HUMAN; BRAF_HUMAN; RAF1_HUMAN	Inhibitor	[1]

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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease

Solid tumour/cancer

ICD Disease Classification

2A00-2F9Z

Molecule Name	Molecule Type	Gene Name	p-value	Fold-Change	Z-score
Raf messenger RNA (Raf mRNA)	DTT	RAF1	2.12E-04	0.49	2.78
B-Raf messenger RNA (BRAF mRNA)	DTT	BRAF	1.56E-01	-0.23	-0.43

Molecular Expression Atlas (MEA)

MEA Detail

Jump to Detail Molecular Expression Atlas of This Drug

References

1	Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
2	ClinicalTrials.gov (NCT01425008) Study of MLN2480 in Patients With Relapsed or Refractory Solid Tumors Followed by a Dose Expansion in Patients With Metastatic Melanoma. U.S. National Institutes of Health.
3	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1943).
4	URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2184).
5	National Cancer Institute Drug Dictionary (drug id 710688).
6	The dual RAF/MEK inhibitor CH5126766/RO5126766 may be a potential therapy for RAS-mutated tumor cells.PLoS One.2014 Nov 25;9(11):e113217.
7	Company report (eli lily)
8	Clinical pipeline report, company report or official report of Roche.
9	Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
10	Combination with liposome-entrapped, ends-modified raf antisense oligonucleotide (LErafAON) improves the anti-tumor efficacies of cisplatin, epirubicin, mitoxantrone, docetaxel and gemcitabine. Anticancer Drugs. 2004 Mar;15(3):243-53.
11	Aldisine alkaloids from the Philippine sponge Stylissa massa are potent inhibitors of mitogen-activated protein kinase kinase-1 (MEK-1). J Med Chem. 2002 Jan 17;45(2):529-32.
12	The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
13	Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.
14	Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
15	The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
16	Novel inhibitors of B-RAF based on a disubstituted pyrazine scaffold. Generation of a nanomolar lead. J Med Chem. 2006 Jan 12;49(1):407-16.
17	US patent application no. 5,981,731, Antisense oligonucleotide modulation of B-raf gene expression.
18	Photoactivatable Prodrugs of Antimelanoma Agent Vemurafenib. ACS Chem Biol. 2015 Sep 18;10(9):2099-107.