Details of the Drug Combination

General Information of Drug Combination (ID: DCQM188)

• Drug Combination Name: Bryostatin-1 + Temsirolimus
• Indication: Recurrent Melanoma; Status: Phase 1 [1]
• Component Drugs:
  Bryostatin-1 (DM1JOXY): Small molecule: 3D MOL is unavailable
  Temsirolimus (DMS104F): Small molecular drug: 3D MOL is unavailable

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Bryostatin-1

Disease Entry	ICD 11	Status	REF
Alzheimer disease	8A20	Phase 2	[2]

Bryostatin-1 Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Protein kinase C epsilon (PRKCE)	TTBZ7OD	KPCE_HUMAN	Activator	[4]
Protein kinase C (PRKC)	TTYVX59	NOUNIPROTAC	Agonist	[5]

Bryostatin-1 Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Protein kinase C gamma type (PRKCG)	OTW52VNZ	KPCG_HUMAN	Decreases Expression	[6]
Protein kinase C beta type (PRKCB)	OTYQ0656	KPCB_HUMAN	Decreases Expression	[6]
Tissue factor (F3)	OT3MSU3B	TF_HUMAN	Increases Expression	[7]
Protein kinase C alpha type (PRKCA)	OT5UWNRD	KPCA_HUMAN	Decreases Expression	[6]
B-cell receptor CD22 (CD22)	OTXDJR9T	CD22_HUMAN	Increases Expression	[8]
Integrin alpha-X (ITGAX)	OTOGIMHE	ITAX_HUMAN	Increases Expression	[8]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Decreases Expression	[9]
Interleukin-12 subunit beta (IL12B)	OT0JF8A3	IL12B_HUMAN	Decreases Expression	[9]
Baculoviral IAP repeat-containing protein 3 (BIRC3)	OT3E95KB	BIRC3_HUMAN	Increases Expression	[10]
TNF receptor-associated factor 1 (TRAF1)	OTTLM5RU	TRAF1_HUMAN	Increases ADR	[11]

Indication(s) of Temsirolimus

Disease Entry	ICD 11	Status	REF
Renal cell carcinoma	2C90	Approved	[3]

Temsirolimus Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Serine/threonine-protein kinase mTOR (mTOR)	TTCJG29	MTOR_HUMAN	Inhibitor	[12]

Temsirolimus Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]

Temsirolimus Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[14]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[14]

References

• [1] ClinicalTrials.gov (NCT00112476) Temsirolimus and Bryostatin 1 in Treating Patients With Unresectable or Metastatic Solid Tumors
• [2] ClinicalTrials.gov (NCT03560245) A Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Assessing the Safety, Tolerability and Efficacy of Bryostatin in the Treatment of Moderately Severe to Severe Alzheimer's Disease Subjects Not Receiving Memantine Treatment. 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. (Ligand id: 5892).
• [4] Protein kinase epsilon dampens the secretory response of model intestinal epithelia during ischemia. Surgery. 2001 Aug;130(2):310-8.
• [5] Bryostatin-1: a promising compound for neurological disorders. Front Pharmacol. 2023 Jun 7;14:1187411.
• [6] Modulation of protein kinase C activity and calcium-sensitive isoform expression in human myeloid leukemia cells by bryostatin 1: relationship to differentiation and ara-C-induced apoptosis. Exp Cell Res. 1996 Oct 10;228(1):65-75. doi: 10.1006/excr.1996.0300.
• [7] Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects. Int J Mol Sci. 2015 Jan 5;16(1):1008-29. doi: 10.3390/ijms16011008.
• [8] Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Clin Cancer Res. 2000 Mar;6(3):825-8.
• [9] Effect of serum and antioxidants on the immunogenicity of protein kinase C-activated chronic lymphocytic leukemia cells. J Immunother. 2005 Jan-Feb;28(1):28-39. doi: 10.1097/00002371-200501000-00004.
• [10] Induction of cIAP-2 in human colon cancer cells through PKC delta/NF-kappa B. J Biol Chem. 2003 Dec 19;278(51):51091-9. doi: 10.1074/jbc.M306541200. Epub 2003 Oct 3.
• [11] 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.
• [12] Advances in kinase targeting: current clinical use and clinical trials. Trends Pharmacol Sci. 2014 Nov;35(11):604-20.
• [13] Association of NR1I2, CYP3A5 and ABCB1 genetic polymorphisms with variability of temsirolimus pharmacokinetics and toxicity in patients with metastatic bladder cancer. Cancer Chemother Pharmacol. 2017 Sep;80(3):653-659.
• [14] Drug Interactions Flockhart Table