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

General Information of Drug (ID: DM2UOSN)

• Drug Name: Conatumumab Drug Info

Indication

Disease Entry	ICD 11	Status	REF
Colorectal cancer	2B91.Z	Phase 2	[1]
Pain	MG30-MG3Z	Discontinued in Phase 2	[2]

• Cross-matching ID: TTD Drug ID: DM2UOSN

Molecule-Related Drug Atlas

Drug(s) Targeting Voltage-gated sodium channel alpha Nav1.8 (SCN10A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Rilpivirine	DMJ0QOW	Human immunodeficiency virus infection	1C62	Approved	[6]
Ropivacaine	DMSPJG2	Anaesthesia	9A78.6	Approved	[7]
Bupivacaine	DM4PRFC	Anaesthesia	9A78.6	Approved	[7]
Tiapride	DMN6CAG	Alcohol dependence	6C40.2	Approved	[8]
Tetracaine	DM9J6C2	Spinal anesthesia	MB40.3	Approved	[9]
Proparacaine	DMLS39E	Anaesthesia	9A78.6	Approved	[7]
VX-150	DMGDB21	Neuropathic pain	8E43.0	Phase 2	[10]
DSP-2230	DM0WTMD	Neuropathic pain	8E43.0	Phase 1	[11]
PF-01247324	DM93LMS	Pain	MG30-MG3Z	Phase 1	[12]
VX-128	DMC8J0G	Pain	MG30-MG3Z	Phase 1	[10]

Drug(s) Targeting TRAIL receptor 2 (TRAIL-R2)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Lexatumumab	DMOS5JZ	Solid tumour/cancer	2A00-2F9Z	Phase 2	[13]
Anti-DR5 cells	DMYKZB3	Hepatocellular carcinoma	2C12.02	Phase 1/2	[14]
IGM-8444	DMFJXDZ	Hematologic tumour	2B33.Y	Phase 1	[15]
INBRX-109	DMUNSPI	Solid tumour/cancer	2A00-2F9Z	Phase 1	[16]
BI 905711	DME9NYV	Solid tumour/cancer	2A00-2F9Z	Phase 1	[17]
DS-8273	DMJPUDW	Colorectal cancer	2B91.Z	Phase 1	[18]
GEN1029	DMV8IWJ	Solid tumour/cancer	2A00-2F9Z	Phase 1	[19]
RhApo2L/TRAIL	DMIAZJ9	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1/2	[4]
LBY-135	DMSRD5U	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[20]
HGS-TR2J	DM0W2TA	Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[21]

Drug(s) Targeting Cannabinoid receptor 1 (CB1)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Marinol	DM70IK5	Anorexia nervosa cachexia	6B80	Approved	[22]
NABILONE	DMVRYT2	Insomnia	7A00-7A0Z	Approved	[23]
Orlistat	DMRJSP8	Obesity	5B81	Approved	[24]
SR141716A	DMCO5JZ	Obesity	5B81	Approved	[25]
Tebipenem	DMVSX6O	Urinary tract infection	GC08	Phase 3	[26]
GW-42004	DMY3KSU	Lipid metabolism disorder	5C52.Z	Phase 2	[27]
SR-147778	DMNAECP	Obesity	5B81	Phase 2	[28]
Nimacimab	DM21Z68	Diabetic nephropathy	GB61.Z	Phase 2	[29]
AEF0117	DMQ1GH4	Marijuana use disorder	6C41	Phase 2	[30]
V-24343	DMJSX9N	Type-2 diabetes	5A11	Phase 1	[31]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Cannabinoid receptor 1 (CB1)	TT6OEDT	CNR1_HUMAN	Agonist	[3]
TRAIL receptor 2 (TRAIL-R2)	TTW20TU	TR10B_HUMAN	Agonist	[4]
Voltage-gated sodium channel alpha Nav1.8 (SCN10A)	TT90XZ8	SCNAA_HUMAN	Binder	[5]

References

• [1] ClinicalTrials.gov (NCT01327612) Open Label Extension Study of Conatumumab and AMG 479. U.S. National Institutes of Health.
• [2] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026807)
• [3] Clinical pipeline report, company report or official report of AstraZeneca (2009).
• [4] Clinical pipeline report, company report or official report of Amgen (2009).
• [5] Pathobiology of visceral pain: molecular mechanisms and therapeutic implications. II. Genetic approaches to pain therapy. Am J Physiol Gastrointest Liver Physiol. 2000 Apr;278(4):G507-12.
• [6] Structures of muO-conotoxins from Conus marmoreus. I nhibitors of tetrodotoxin (TTX)-sensitive and TTX-resistant sodium channels in mammalian senso... J Biol Chem. 2004 Jun 11;279(24):25774-82.
• [7] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [8] Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
• [9] Heterologous expression and functional analysis of rat Nav1.8 (SNS) voltage-gated sodium channels in the dorsal root ganglion neuroblastoma cell line ND7-23. Neuropharmacology. 2004 Mar;46(3):425-38.
• [10] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [11] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [12] Oral Administration of PF-01247324, a Subtype-Selective Nav1.8 Blocker, Reverses Cerebellar Deficits in a Mouse Model of Multiple Sclerosis. PLoS One. 2015; 10(3): e0119067.
• [13] National Cancer Institute Drug Dictionary (drug id 528015).
• [14] ClinicalTrials.gov (NCT03638206) Autologous CAR-T/TCR-T Cell Immunotherapy for Malignancies
• [15] Clinical pipeline report, company report or official report of IGM Biosciences.
• [16] Clinical pipeline report, company report or official report of Inhibrx.
• [17] Selective Tumor Cell Apoptosis and Tumor Regression in CDH17-Positive Colorectal Cancer Models using BI 905711, a Novel Liver-Sparing TRAILR2 Agonist. Mol Cancer Ther. 2021 Jan;20(1):96-108.
• [18] First-in-human study of the antibody DR5 agonist DS-8273a in patients with advanced solid tumors. Invest New Drugs. 2017 Jun;35(3):298-306.
• [19] National Cancer Institute Drug Dictionary (drug name Tilogotamab).
• [20] Safety, pharmacokinetics, and pharmacodynamics of the DR5 antibody LBY135 alone and in combination with capecitabine in patients with advanced solid tumors. Invest New Drugs. 2014 Feb;32(1):135-44.
• [21] Enhancement of Glioma Radiation Therapy and Chemotherapy Response with Targeted Antibody Therapy Against Death Receptor 5. Int J Radiat Oncol Biol Phys. 2008 June 1; 71(2): 507-516.
• [22] Emerging strategies for exploiting cannabinoid receptor agonists as medicines. Br J Pharmacol. 2009 Feb;156(3):397-411.
• [23] Novel 1',1'-chain substituted hexahydrocannabinols: 9-hydroxy-3-(1-hexyl-cyclobut-1-yl)-hexahydrocannabinol (AM2389) a highly potent cannabinoid r... J Med Chem. 2010 Oct 14;53(19):6996-7010.
• [24] Tetrahydrolipstatin analogues as modulators of endocannabinoid 2-arachidonoylglycerol metabolism. J Med Chem. 2008 Nov 13;51(21):6970-9.
• [25] Anti-obesity drugs. Expert Opin Pharmacother. 2008 Jun;9(8):1339-50.
• [26] Emerging drugs for obesity: linking novel biological mechanisms to pharmaceutical pipelines. Expert Opin Emerg Drugs. 2005 Aug;10(3):643-60.
• [27] Company report (Gwpharm)
• [28] Surinabant, a selective cannabinoid receptor type 1 antagonist, inhibits 9-tetrahydrocannabinol-induced central nervous system and heart rate effects in humans.Br J Clin Pharmacol.2013 Jul;76(1):65-77.
• [29] Clinical pipeline report, company report or official report of Bird Rock Bio.
• [30] Clinical pipeline report, company report or official report of Affimed Therapeutics.
• [31] Cannabinoid receptor antagonists: pharmacological opportunities, clinical experience, and translational prognosis. Expert Opin Emerg Drugs. 2009 Mar;14(1):43-65.