Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMBR8NF)

• Drug Name: MLN2480 Drug Info
• 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]

• Cross-matching ID:
  PubChem CID: 25161177
  CAS Number: CAS 1096708-71-2
  TTD Drug ID: DMBR8NF

Molecule-Related Drug Atlas

Drug(s) Targeting Serine/threonine-protein kinase Raf (RAF)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RO-5126766	DM3U9BY	Non-small-cell lung cancer	2C25	Phase 2	[5]
LY3009120	DM6PFCN	Solid tumour/cancer	2A00-2F9Z	Phase 1	[6]

Drug(s) Targeting Raf messenger RNA (Raf mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
SPN-803	DM8O2AQ	Parkinson disease	8A00.0	Phase 1	[4]
LXH254	DMQE9PS	Non-small-cell lung cancer	2C25.Y	Phase 1	[1]
ICo-007	DM79W8K	Diabetic macular edema	9B71.02	Phase 1	[8]
LErafAON	DMNHPOT	Solid tumour/cancer	2A00-2F9Z	Phase 1	[9]
DEBROMOHYMENIALDISINE	DMDLER8	Discovery agent	N.A.	Investigative	[10]
ZM-336372	DMD5JYQ	Discovery agent	N.A.	Investigative	[11]
6-[(E)-2-(4-Fluoro-phenyl)-vinyl]-9H-purine	DMDNG8F	Discovery agent	N.A.	Investigative	[12]
PLX-ORI3	DMZG1L5	Solid tumour/cancer	2A00-2F9Z	Investigative	[4]
6-Benzylsulfanyl-9H-purine	DMI7FNZ	Discovery agent	N.A.	Investigative	[12]

Drug(s) Targeting B-Raf messenger RNA (BRAF mRNA)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RG7304	DMGFAVQ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[7]
SPN-803	DM8O2AQ	Parkinson disease	8A00.0	Phase 1	[3]
PLX-4720	DMBK9AM	Cutaneous melanoma	2C30	Phase 1	[13]
L-779450	DM51B74	Discovery agent	N.A.	Investigative	[14]
ZM-336372	DMD5JYQ	Discovery agent	N.A.	Investigative	[11]
PLX-ORI3	DMZG1L5	Solid tumour/cancer	2A00-2F9Z	Investigative	[3]
2-(Phenylamino)-6-(3-acetamidophenyl)pyrazine	DMPUARE	Discovery agent	N.A.	Investigative	[15]
ISIS 13741	DMC7Q38	Discovery agent	N.A.	Investigative	[16]
ISIS 14144	DMWIKD5	Discovery agent	N.A.	Investigative	[16]
PMID26061392C2	DMHZOIU	Discovery agent	N.A.	Investigative	[17]

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]
Serine/threonine-protein kinase Raf (RAF)	TTQ9K3Y	ARAF_HUMAN; BRAF_HUMAN; RAF1_HUMAN	Inhibitor	[1]

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] 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.
• [6] Company report (eli lily)
• [7] Clinical pipeline report, company report or official report of Roche.
• [8] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2009).
• [9] 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.
• [10] 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.
• [11] The selectivity of protein kinase inhibitors: a further update. Biochem J. 2007 Dec 15;408(3):297-315.
• [12] Synthesis and biological testing of purine derivatives as potential ATP-competitive kinase inhibitors. J Med Chem. 2005 Feb 10;48(3):710-22.
• [13] Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol. 2011 Oct 30;29(11):1046-51.
• [14] The identification of potent and selective imidazole-based inhibitors of B-Raf kinase. Bioorg Med Chem Lett. 2006 Jan 15;16(2):378-81.
• [15] 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.
• [16] US patent application no. 5,981,731, Antisense oligonucleotide modulation of B-raf gene expression.
• [17] Photoactivatable Prodrugs of Antimelanoma Agent Vemurafenib. ACS Chem Biol. 2015 Sep 18;10(9):2099-107.