Details of the Drug Combination

General Information of Drug Combination (ID: DCJN7YB)

Drug Combination Name

GDC-0152 Caffeine

Indication

Disease Entry	Status	REF
Amyotrophic Lateral Sclerosis	Phase 1	[1]

Component Drugs

GDC-0152 DM1B3UM

Caffeine DMKBJWP

Small molecular drug

2D MOL

3D MOL is unavailable

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of GDC-0152

Disease Entry	ICD 11	Status	REF
Obesity	5B81	Phase 1	[2]
Solid tumour/cancer	2A00-2F9Z	Discontinued in Phase 1	[3]

GDC-0152 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
X-linked inhibitor of apoptosis protein (XIAP)	TTR7B60	XIAP_HUMAN	Modulator	[2]
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Indication(s) of Caffeine

Disease Entry	ICD 11	Status	REF
Allergic rhinitis	CA08.0	Approved	[4]
Back pain	ME84.Z	Approved	[4]
Cluster headache	8A81.0	Approved	[4]
Common cold	CA00	Approved	[4]
Dysmenorrhea	GA34.3	Approved	[4]
Headache	8A80-8A84	Approved	[4]
Migraine disorder	N.A.	Approved	[4]
Orthostatic hypotension	BA21	Approved	[5]
Pain	MG30-MG3Z	Approved	[4]

Caffeine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Adenosine A2a receptor (ADORA2A)	TTM2AOE	AA2AR_HUMAN	Antagonist	[6]
Adenosine A1 receptor (ADORA1)	TTK25J1	AA1R_HUMAN	Antagonist	[6]
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Caffeine Interacts with 8 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[8]
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[9]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[10]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Metabolism	[11]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[12]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[13]
Cytochrome P450 1B1 (CYP1B1)	DE9QHP6	CP1B1_HUMAN	Metabolism	[14]
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⏷ Show the Full List of 8 DME(s)

Caffeine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	OTLLBX48	CP1A2_HUMAN	Increases ADR	[15]
Metallothionein-1A (MT1A)	OTKBH52X	MT1A_HUMAN	Increases ADR	[16]
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References

1	ClinicalTrials.gov (NCT02655614) A Study of GDC-0134 to Determine Initial Safety, Tolerability, and Pharmacokinetic Parameters in Participants With Amyotrophic Lateral Sclerosis
2	Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem. 2012 May 10;55(9):4101-13.
3	Small molecules, big targets: drug discovery faces the protein-protein interaction challenge.Nat Rev Drug Discov. 2016 Aug;15(8):533-50.
4	Caffeine FDA Label
5	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. (Ligand id: 407).
6	Caffeine as a psychomotor stimulant: mechanism of action. Cell Mol Life Sci. 2004 Apr;61(7-8):857-72.
7	Effect of cytochrome P450 (CYP) inducers on caffeine metabolism in the rat. Pharmacol Rep. 2007 May-Jun;59(3):296-305.
8	Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
9	A population and family study of N-acetyltransferase using caffeine urinary metabolites. Clin Pharmacol Ther. 1993 Aug;54(2):134-41.
10	Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo. J Clin Psychopharmacol. 1998 Jun;18(3):198-207.
11	CYP2E1 active site residues in substrate recognition sequence 5 identified by photoaffinity labeling and homology modeling. Arch Biochem Biophys. 2007 Mar 1;459(1):59-69.
12	PharmGKB summary: caffeine pathway. Pharmacogenet Genomics. 2012 May;22(5):389-95.
13	Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline. Xenobiotica. 2013 Dec;43(12):1037-42.
14	Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos. 1997 May;25(5):617-22.
15	Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006 Mar 8;295(10):1135-41. doi: 10.1001/jama.295.10.1135.
16	ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.