Details of the Drug Combination

General Information of Drug Combination (ID: DC310V0)

• Drug Combination Name: Clindamycin + Clotrimazole
• Indication: Candidiasis; Status: Phase 4 [1]
• Component Drugs:
  Clindamycin (DM15HL8): Small molecular drug
  Clotrimazole (DMMFCIH): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Clindamycin

Disease Entry	ICD 11	Status	REF
Acne vulgaris	ED80	Approved	[2]
Aspiration pneumonia	N.A.	Approved	[3]
Bacteremia	1A73	Approved	[3]
Bacterial vaginosis	MF3A	Approved	[3]
Pleural empyema	N.A.	Approved	[3]
Staphylococcal pneumonia	N.A.	Approved	[3]
Staphylococcus aureus infection	N.A.	Approved	[3]
Streptococcal pneumonia	N.A.	Approved	[3]
Pelvic inflammatory disease	GA05	Investigative	[3]

Clindamycin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial 50S ribosomal RNA (Bact 50S rRNA)	TTUWYEA	NOUNIPROTAC	Binder	[6]

Clindamycin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Beta-lactamase (blaB)	DEMSNER	A4LA84_EDWTA	Metabolism	[8]

Clindamycin Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[9]
Collagenase 3 (MMP13)	OTY8BZIE	MMP13_HUMAN	Increases Expression	[10]

Indication(s) of Clotrimazole

Disease Entry	ICD 11	Status	REF
Cutaneous candidiasis	1F23.14	Approved	[4]
Fungal infection	1F29-1F2F	Approved	[5]
Mycoses	1F2Z	Approved	[4]
Oral candidiasis	1F23.0	Approved	[4]
Tinea corporis	1F28.Y	Approved	[4]
Tinea cruris	1F28.3	Approved	[4]
Tinea versicolor	1F2D.0	Approved	[4]
Tinea pedis	1F28.2	Investigative	[4]

Clotrimazole Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
C-X-C chemokine receptor type 2 (CXCR2)	TT30C9G	CXCR2_HUMAN	Modulator	[13]

Clotrimazole Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]

Clotrimazole Interacts with 17 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Increases Expression	[15]
Nuclear receptor subfamily 1 group I member 2 (NR1I2)	OTC5U0N5	NR1I2_HUMAN	Increases Expression	[16]
Nuclear receptor subfamily 1 group I member 3 (NR1I3)	OTS3SGH7	NR1I3_HUMAN	Decreases Activity	[17]
Bile salt export pump (ABCB11)	OTRU7THO	ABCBB_HUMAN	Decreases Activity	[18]
ATP-binding cassette sub-family C member 3 (ABCC3)	OTC3IJV4	MRP3_HUMAN	Increases Expression	[19]
Intermediate conductance calcium-activated potassium channel protein 4 (KCNN4)	OTQKQ346	KCNN4_HUMAN	Decreases Activity	[20]
Adenylate cyclase type 9 (ADCY9)	OT1IZT5K	ADCY9_HUMAN	Decreases Activity	[21]
Protein c-Fos (FOS)	OTJBUVWS	FOS_HUMAN	Decreases Expression	[22]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[22]
ATP-dependent 6-phosphofructokinase, muscle type (PFKM)	OT1QY9JM	PFKAM_HUMAN	Decreases Expression	[11]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Increases Expression	[23]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Increases Expression	[22]
Cyclin-dependent kinase inhibitor 1 (CDKN1A)	OTQWHCZE	CDN1A_HUMAN	Decreases Expression	[24]
Cyclin-dependent kinase inhibitor 1B (CDKN1B)	OTNY5LLZ	CDN1B_HUMAN	Increases Expression	[24]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[25]
Eukaryotic translation initiation factor 2A (EIF2A)	OTWXELQP	EIF2A_HUMAN	Increases Phosphorylation	[26]
DnaJ homolog subfamily B member 4 (DNAJB4)	OTUD01BK	DNJB4_HUMAN	Increases Expression	[23]

References

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• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Clindamycin FDA Label
• [4] Clotrimazole FDA Label
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• [15] Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol. 1996 Feb;49(2):311-8.
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• [19] Activation of p38 Mitogen-Activated Protein Kinase by Clotrimazole Induces Multidrug Resistance-Associated Protein 3 Activation through a Novel Transcriptional Element. J Pharmacol Exp Ther. 2016 Oct;359(1):102-9. doi: 10.1124/jpet.115.231589. Epub 2016 Aug 9.
• [20] Functional and molecular identification of intermediate-conductance Ca(2+)-activated K(+) channels in breast cancer cells: association with cell cycle progression. Am J Physiol Cell Physiol. 2004 Jul;287(1):C125-34. doi: 10.1152/ajpcell.00488.2003. Epub 2004 Feb 25.
• [21] Direct stimulation of adenylyl cyclase 9 by the fungicide imidazole miconazole. Naunyn Schmiedebergs Arch Pharmacol. 2019 Apr;392(4):497-504. doi: 10.1007/s00210-018-01610-1. Epub 2019 Jan 3.
• [22] Effects of clotrimazole on the growth, morphological characteristics, and cisplatin sensitivity of human glioblastoma cells in vitro. J Neurosurg. 1999 May;90(5):918-27. doi: 10.3171/jns.1999.90.5.0918.
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• [25] A Gene Expression Biomarker Predicts Heat Shock Factor 1 Activation in a Gene Expression Compendium. Chem Res Toxicol. 2021 Jul 19;34(7):1721-1737. doi: 10.1021/acs.chemrestox.0c00510. Epub 2021 Jun 25.
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