This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.
Identification
- Generic Name
- Bryostatin 1
- DrugBank Accession Number
- DB11752
- Background
Bryostatin 1 has been investigated for the treatment of HIV Infection and Alzheimer's Disease.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Bryostatin 1 (DB11752)
- Weight
- Average: 905.044
Monoisotopic: 904.44565073 - Chemical Formula
- C47H68O17
- Synonyms
- Bryostatin-1
Pharmacology
- Indication
Not Available
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Target Actions Organism UProtein kinase C alpha type activatorHumans UProtein kinase C epsilon type activatorHumans UCaspase-8 inhibitorHumans USerine/threonine-protein kinase D1 activatorHumans UT-lymphocyte activation antigen CD86 inducerHumans UProstaglandin G/H synthase 2 inducerHumans UG1/S-specific cyclin-D1 inhibitorHumans UTumor necrosis factor inducerHumans UProtein unc-13 homolog B ligandMouse - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Bryostatin 1. Acalabrutinib The serum concentration of Acalabrutinib can be increased when it is combined with Bryostatin 1. Acenocoumarol The serum concentration of Acenocoumarol can be increased when it is combined with Bryostatin 1. Acetyldigitoxin The serum concentration of Acetyldigitoxin can be increased when it is combined with Bryostatin 1. Albendazole The metabolism of Albendazole can be decreased when combined with Bryostatin 1. - Food Interactions
- No interactions found.
Categories
- Drug Categories
- Adjuvants, Immunologic
- Anti-Bacterial Agents
- Antineoplastic Agents
- Biological Factors
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Enzyme Activation
- Ethers
- Ethers, Cyclic
- Immunologic Factors
- Lactones
- Macrolides
- Marine Toxins
- Polyether Polyketides
- Polyether Toxins
- Toxins, Biological
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 37O2X55Y9E
- CAS number
- 83314-01-6
- InChI Key
- MJQUEDHRCUIRLF-TVIXENOKSA-N
- InChI
- InChI=1S/C47H68O17/c1-10-11-12-13-14-15-39(51)62-43-31(22-41(53)58-9)21-34-25-37(28(2)48)61-42(54)24-32(50)23-35-26-38(59-29(3)49)45(6,7)46(55,63-35)27-36-19-30(20-40(52)57-8)18-33(60-36)16-17-44(4,5)47(43,56)64-34/h12-17,20,22,28,32-38,43,48,50,55-56H,10-11,18-19,21,23-27H2,1-9H3/b13-12+,15-14+,17-16+,30-20+,31-22+/t28-,32-,33+,34+,35-,36+,37-,38+,43+,46+,47-/m1/s1
- IUPAC Name
- (1S,3S,5Z,7R,8E,11S,12S,13E,15S,17R,21R,23R,25S)-25-(acetyloxy)-1,11,21-trihydroxy-17-[(1R)-1-hydroxyethyl]-5,13-bis(2-methoxy-2-oxoethylidene)-10,10,26,26-tetramethyl-19-oxo-18,27,28,29-tetraoxatetracyclo[21.3.1.1^{3,7}.1^{11,15}]nonacos-8-en-12-yl (2E,4E)-octa-2,4-dienoate
- SMILES
- [H][C@]12C[C@H](OC(C)=O)C(C)(C)[C@](O)(C[C@]3([H])C\C(C[C@@]([H])(O3)\C=C\C(C)(C)[C@]3(O)O[C@@]([H])(C\C(=C/C(=O)OC)[C@@H]3OC(=O)\C=C\C=C\CCC)C[C@@]([H])(OC(=O)C[C@H](O)C1)[C@@H](C)O)=C\C(=O)OC)O2
References
- General References
- Not Available
- External Links
- PubChem Compound
- 22524140
- PubChem Substance
- 347828109
- ChemSpider
- 10196541
- BindingDB
- 50258529
- ChEBI
- 88353
- ChEMBL
- CHEMBL449158
- ZINC
- ZINC000169357315
- Wikipedia
- Bryostatin
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00595 mg/mL ALOGPS logP 2.86 ALOGPS logP 5.04 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 10.59 Chemaxon pKa (Strongest Basic) -2.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 12 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 240.11 Å2 Chemaxon Rotatable Bond Count 13 Chemaxon Refractivity 233.05 m3·mol-1 Chemaxon Polarizability 95.4 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 315.3498653 predictedDarkChem Lite v0.1.0 [M-H]- 317.9814653 predictedDarkChem Lite v0.1.0 [M+H]+ 317.3513653 predictedDarkChem Lite v0.1.0
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Activator
- General Function
- Zinc ion binding
- Specific Function
- Calcium-activated, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that is involved in positive and negative regulation of cell proliferation, apoptosis, differenti...
- Gene Name
- PRKCA
- Uniprot ID
- P17252
- Uniprot Name
- Protein kinase C alpha type
- Molecular Weight
- 76749.445 Da
References
- Khan TK, Nelson TJ: Protein kinase C activator bryostatin-1 modulates proteasome function. J Cell Biochem. 2018 Aug;119(8):6894-6904. doi: 10.1002/jcb.26887. Epub 2018 Apr 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Activator
- General Function
- Signal transducer activity
- Specific Function
- Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that plays essential roles in the regulation of multiple cellular processes linked to cytoskele...
- Gene Name
- PRKCE
- Uniprot ID
- Q02156
- Uniprot Name
- Protein kinase C epsilon type
- Molecular Weight
- 83673.2 Da
References
- Khan TK, Nelson TJ: Protein kinase C activator bryostatin-1 modulates proteasome function. J Cell Biochem. 2018 Aug;119(8):6894-6904. doi: 10.1002/jcb.26887. Epub 2018 Apr 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Ubiquitin protein ligase binding
- Specific Function
- Most upstream protease of the activation cascade of caspases responsible for the TNFRSF6/FAS mediated and TNFRSF1A induced cell death. Binding to the adapter molecule FADD recruits it to either rec...
- Gene Name
- CASP8
- Uniprot ID
- Q14790
- Uniprot Name
- Caspase-8
- Molecular Weight
- 55390.53 Da
References
- Khan TK, Nelson TJ: Protein kinase C activator bryostatin-1 modulates proteasome function. J Cell Biochem. 2018 Aug;119(8):6894-6904. doi: 10.1002/jcb.26887. Epub 2018 Apr 25. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Activator
- General Function
- Serine/threonine-protein kinase that converts transient diacylglycerol (DAG) signals into prolonged physiological effects downstream of PKC, and is involved in the regulation of MAPK8/JNK1 and Ras signaling, Golgi membrane integrity and trafficking, cell survival through NF-kappa-B activation, cell migration, cell differentiation by mediating HDAC7 nuclear export, cell proliferation via MAPK1/3 (ERK1/2) signaling, and plays a role in cardiac hypertrophy, VEGFA-induced angiogenesis, genotoxic-induced apoptosis and flagellin-stimulated inflammatory response. Phosphorylates the epidermal growth factor receptor (EGFR) on dual threonine residues, which leads to the suppression of epidermal growth factor (EGF)-induced MAPK8/JNK1 activation and subsequent JUN phosphorylation. Phosphorylates RIN1, inducing RIN1 binding to 14-3-3 proteins YWHAB, YWHAE and YWHAZ and increased competition with RAF1 for binding to GTP-bound form of Ras proteins (NRAS, HRAS and KRAS). Acts downstream of the heterotrimeric G-protein beta/gamma-subunit complex to maintain the structural integrity of the Golgi membranes, and is required for protein transport along the secretory pathway. In the trans-Golgi network (TGN), regulates the fission of transport vesicles that are on their way to the plasma membrane. May act by activating the lipid kinase phosphatidylinositol 4-kinase beta (PI4KB) at the TGN for the local synthesis of phosphorylated inositol lipids, which induces a sequential production of DAG, phosphatidic acid (PA) and lyso-PA (LPA) that are necessary for membrane fission and generation of specific transport carriers to the cell surface. Under oxidative stress, is phosphorylated at Tyr-463 via SRC-ABL1 and contributes to cell survival by activating IKK complex and subsequent nuclear translocation and activation of NFKB1. Involved in cell migration by regulating integrin alpha-5/beta-3 recycling and promoting its recruitment in newly forming focal adhesion. In osteoblast differentiation, mediates the bone morphogenetic protein 2 (BMP2)-induced nuclear export of HDAC7, which results in the inhibition of HDAC7 transcriptional repression of RUNX2. In neurons, plays an important role in neuronal polarity by regulating the biogenesis of TGN-derived dendritic vesicles, and is involved in the maintenance of dendritic arborization and Golgi structure in hippocampal cells. May potentiate mitogenesis induced by the neuropeptide bombesin or vasopressin by mediating an increase in the duration of MAPK1/3 (ERK1/2) signaling, which leads to accumulation of immediate-early gene products including FOS that stimulate cell cycle progression. Plays an important role in the proliferative response induced by low calcium in keratinocytes, through sustained activation of MAPK1/3 (ERK1/2) pathway. Downstream of novel PKC signaling, plays a role in cardiac hypertrophy by phosphorylating HDAC5, which in turn triggers XPO1/CRM1-dependent nuclear export of HDAC5, MEF2A transcriptional activation and induction of downstream target genes that promote myocyte hypertrophy and pathological cardiac remodeling. Mediates cardiac troponin I (TNNI3) phosphorylation at the PKA sites, which results in reduced myofilament calcium sensitivity, and accelerated crossbridge cycling kinetics. The PRKD1-HDAC5 pathway is also involved in angiogenesis by mediating VEGFA-induced specific subset of gene expression, cell migration, and tube formation. In response to VEGFA, is necessary and required for HDAC7 phosphorylation which induces HDAC7 nuclear export and endothelial cell proliferation and migration. During apoptosis induced by cytarabine and other genotoxic agents, PRKD1 is cleaved by caspase-3 at Asp-378, resulting in activation of its kinase function and increased sensitivity of cells to the cytotoxic effects of genotoxic agents. In epithelial cells, is required for transducing flagellin-stimulated inflammatory responses by binding and phosphorylating TLR5, which contributes to MAPK14/p38 activation and production of inflammatory cytokines. May play a role in inflammatory response by mediating activation of NF-kappa-B. May be involved in pain transmission by directly modulating TRPV1 receptor. Plays a role in activated KRAS-mediated stabilization of ZNF304 in colorectal cancer (CRC) cells (PubMed:24623306). Regulates nuclear translocation of transcription factor TFEB in macrophages upon live S.enterica infection (By similarity).
- Specific Function
- Atp binding
- Gene Name
- PRKD1
- Uniprot ID
- Q15139
- Uniprot Name
- Serine/threonine-protein kinase D1
- Molecular Weight
- 101703.275 Da
References
- Jaggi M, Chauhan SC, Du C, Balaji KC: Bryostatin 1 modulates beta-catenin subcellular localization and transcription activity through protein kinase D1 activation. Mol Cancer Ther. 2008 Sep;7(9):2703-12. doi: 10.1158/1535-7163.MCT-08-0119. Epub 2008 Sep 2. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Virus receptor activity
- Specific Function
- Receptor involved in the costimulatory signal essential for T-lymphocyte proliferation and interleukin-2 production, by binding CD28 or CTLA-4. May play a critical role in the early events of T-cel...
- Gene Name
- CD86
- Uniprot ID
- P42081
- Uniprot Name
- T-lymphocyte activation antigen CD86
- Molecular Weight
- 37681.97 Da
References
- Kornberg MD, Smith MD, Shirazi HA, Calabresi PA, Snyder SH, Kim PM: Bryostatin-1 alleviates experimental multiple sclerosis. Proc Natl Acad Sci U S A. 2018 Feb 27;115(9):2186-2191. doi: 10.1073/pnas.1719902115. Epub 2018 Feb 12. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Prostaglandin-endoperoxide synthase activity
- Specific Function
- Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Constitutively expressed in some tissues in physiological conditions, such as the endothelium, kidney and...
- Gene Name
- PTGS2
- Uniprot ID
- P35354
- Uniprot Name
- Prostaglandin G/H synthase 2
- Molecular Weight
- 68995.625 Da
References
- De Lorenzo MS, Yamaguchi K, Subbaramaiah K, Dannenberg AJ: Bryostatin-1 stimulates the transcription of cyclooxygenase-2: evidence for an activator protein-1-dependent mechanism. Clin Cancer Res. 2003 Oct 15;9(13):5036-43. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Transcription factor binding
- Specific Function
- Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S t...
- Gene Name
- CCND1
- Uniprot ID
- P24385
- Uniprot Name
- G1/S-specific cyclin-D1
- Molecular Weight
- 33728.74 Da
References
- Wang J, Wang Z, Sun Y, Liu D: Bryostatin-1 inhibits cell proliferation of hepatocarcinoma and induces cell cycle arrest by activation of GSK3beta. Biochem Biophys Res Commun. 2019 May 7;512(3):473-478. doi: 10.1016/j.bbrc.2019.03.014. Epub 2019 Mar 20. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Tumor necrosis factor receptor binding
- Specific Function
- Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct ac...
- Gene Name
- TNF
- Uniprot ID
- P01375
- Uniprot Name
- Tumor necrosis factor
- Molecular Weight
- 25644.15 Da
References
- Kedei N, Kraft MB, Keck GE, Herald CL, Melody N, Pettit GR, Blumberg PM: Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships. J Nat Prod. 2015 Apr 24;78(4):896-900. doi: 10.1021/acs.jnatprod.5b00094. Epub 2015 Mar 26. [Article]
- Kind
- Protein
- Organism
- Mouse
- Pharmacological action
- Unknown
- Actions
- Ligand
- General Function
- Plays a role in vesicle maturation during exocytosis as a target of the diacylglycerol second messenger pathway. Is involved in neurotransmitter release by acting in synaptic vesicle priming prior to vesicle fusion and participates in the activity-depending refilling of readily releasable vesicle pool (RRP) (By similarity). Essential for synaptic vesicle maturation in a subset of excitatory/glutamatergic but not inhibitory/GABA-mediated synapses. In collaboration with UNC13A, facilitates neuronal dense core vesicles fusion as well as controls the location and efficiency of their synaptic release (PubMed:23229896).
- Specific Function
- Calcium ion binding
- Gene Name
- Unc13b
- Uniprot ID
- Q9Z1N9
- Uniprot Name
- Protein unc-13 homolog B
- Molecular Weight
- 181811.505 Da
References
- Blanco FA, Czikora A, Kedei N, You Y, Mitchell GA, Pany S, Ghosh A, Blumberg PM, Das J: Munc13 Is a Molecular Target of Bryostatin 1. Biochemistry. 2019 Jul 9;58(27):3016-3030. doi: 10.1021/acs.biochem.9b00427. Epub 2019 Jun 20. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Kuper JI, D'Aprile M: Drug-Drug interactions of clinical significance in the treatment of patients with Mycobacterium avium complex disease. Clin Pharmacokinet. 2000 Sep;39(3):203-14. doi: 10.2165/00003088-200039030-00003. [Article]
Drug created at October 20, 2016 20:45 / Updated at December 01, 2022 11:27