This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

Name
Bryostatin 1
Accession Number
DB11752
Description

Bryostatin 1 has been investigated for the treatment of HIV Infection and Alzheimer's Disease.

Type
Small Molecule
Groups
Investigational
Synonyms
Not Available

Pharmacology

Indication
Not Available
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics
Not Available
Mechanism of action
TargetActionsOrganism
UProtein kinase C alpha type
activator
Humans
UProtein kinase C epsilon type
activator
Humans
UCaspase-8
inhibitor
Humans
USerine/threonine-protein kinase D1
activator
Humans
UT-lymphocyte activation antigen CD86
inducer
Humans
UProstaglandin G/H synthase 2
inducer
Humans
UG1/S-specific cyclin-D1
inhibitor
Humans
UTumor necrosis factor
inducer
Humans
UProtein unc-13 homolog B
ligand
Mouse
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
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Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
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.
DrugInteraction
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Bryostatin 1.
AcalabrutinibThe metabolism of Acalabrutinib can be decreased when combined with Bryostatin 1.
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Bryostatin 1.
AcetyldigitoxinThe serum concentration of Acetyldigitoxin can be increased when it is combined with Bryostatin 1.
AlbendazoleThe metabolism of Albendazole can be decreased when combined with Bryostatin 1.
AlectinibThe metabolism of Alectinib can be decreased when combined with Bryostatin 1.
AlfentanilThe serum concentration of Alfentanil can be increased when it is combined with Bryostatin 1.
AlfuzosinThe metabolism of Alfuzosin can be decreased when combined with Bryostatin 1.
AlpelisibThe metabolism of Alpelisib can be decreased when combined with Bryostatin 1.
AlprazolamThe metabolism of Alprazolam can be decreased when combined with Bryostatin 1.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
No interactions found.

Products

Categories

Drug Categories
Classification
Not classified

Chemical Identifiers

UNII
37O2X55Y9E
CAS number
83314-01-6
InChI Key
Not Available
InChI
Not Available
IUPAC Name
Not Available
SMILES
Not Available

References

General References
Not Available
PubChem Compound
22524140
PubChem Substance
347828109
ChemSpider
4444327
Wikipedia
Bryostatin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentAcinar Cell Adenocarcinoma of the Pancreas / Duct Cell Adenocarcinoma of the Pancreas / Recurrent Pancreatic Cancer / Stage III Pancreatic Cancer / Stage IV Pancreatic Cancer1
2CompletedTreatmentAcute Myeloid Leukemia (AML) / Myelodysplastic Syndrome1
2CompletedTreatmentAdvanced Gastric Cancer / Stage III Gastric Cancer1
2CompletedTreatmentAlzheimer's Disease (AD)1
2CompletedTreatmentBreast Cancer1
2CompletedTreatmentCervical Cancers1
2CompletedTreatmentColorectal Cancers1
2CompletedTreatmentEsophageal Cancers / Malignant Neoplasm of Stomach2
2CompletedTreatmentExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue / Nodal marginal zone B-cell lymphomas / Recurrent Adult Diffuse Large Cell Lymphoma / Recurrent Adult Diffuse Mixed Cell Lymphoma / Recurrent Adult Diffuse Small Cleaved Cell Lymphoma / Recurrent Grade 1 Follicular Lymphoma / Recurrent Grade 2 Follicular Lymphoma / Recurrent Grade 3 Follicular Lymphoma / Recurrent Mantle Cell Lymphoma / Recurrent Marginal Zone Lymphoma / Recurrent Small Lymphocytic Lymphoma / Splenic Marginal Zone Lymphoma1
2CompletedTreatmentFallopian Tube Cancer / Primary Peritoneal Cavity Cancer / Recurrent Ovarian Epithelial Cancer / Stage III Ovarian Epithelial Cancer / Stage IV Ovarian Epithelial Cancer1

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
Not Available
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Targets

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
  1. 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. [PubMed:29693282]
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
  1. 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. [PubMed:29693282]
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
  1. 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. [PubMed:29693282]
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
  1. 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. [PubMed:18765827]
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
  1. 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. [PubMed:29440425]
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
  1. 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. [PubMed:14581379]
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
  1. 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. [PubMed:30904158]
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
  1. 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. [PubMed:25808573]
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
  1. 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. [PubMed:31243993]

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
  1. 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. [PubMed:11020135]

Drug created on October 20, 2016 14:45 / Updated on June 12, 2020 10:53

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