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Details

Stereochemistry ABSOLUTE
Molecular Formula C47H68O17
Molecular Weight 905.0344
Optical Activity UNSPECIFIED
Defined Stereocenters 11 / 11
E/Z Centers 4
Charge 0

SHOW SMILES / InChI
Structure of BRYOSTATIN 1

SMILES

CCC/C(/[H])=C(\[H])/C(/[H])=C(\[H])/C(=O)O[C@@]1([H])/C(=C(\[H])/C(=O)OC)/C[C@@]2([H])C[C@]([H])([C@@]([H])(C)O)OC(=O)C[C@@]([H])(C[C@]3([H])C[C@@]([H])(C(C)(C)[C@@](C[C@]4([H])C/C(=C(\[H])/C(=O)OC)/C[C@]([H])(/C(/[H])=C(\[H])/C(C)(C)[C@]1(O)O2)O4)(O)O3)OC(=O)C)O

InChI

InChIKey=MJQUEDHRCUIRLF-TVIXENOKSA-N
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

HIDE SMILES / InChI

Molecular Formula C47H68O17
Molecular Weight 905.0344
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 11 / 11
E/Z Centers 4
Optical Activity UNSPECIFIED

Bryostatin 1 is a macrocyclic lactone which can be isolated from the marine bryozoan, Bugula neritina. The effects of bryostatin 1 are attributed to its ability to selectively modulate the activity of two of the three subgroups of protein kinase C (PKC) isozymes. PKC isozymes are divided into three subgroups which differ in their molecular structures and co-factor requirements: classical PKC (cPKC), novel PKC (nPKC), and atypical PKC (aPKC). Bryostatin-1 modulates nPKC activity independent of a Ca2+ signaling. It activates cPKC only when associated with Ca2+ signaling. And, aPKC activity is not sensitive to bryostatin-1 administration. Ca2+ signals play an important role in synaptic transmission and information processing which creates a biological environment where Bryostatin-1 possesses a unique action profile. Bryostatin-1 will not affect cPKC activity in neurons which are not functioning as an active part of the signaling processing circuit with significant Ca2+influx and intracellular Ca2+ release. Bryostatin 1 is in phase II clinical trials for investigation as an anticancer agent; specifically for treatment of metastatic or recurrent head and neck cancer, ovarian epithelial cancer that has not responded to previous chemotherapy, and myelodysplastic syndrome. Bryostatin 1 has also generated interest as an investigational compound for the treatment of Alzheimer's disease.

CNS Activity

Curator's Comment:: bryostatin-1 can pass through the blood-brain barrier, although the brain levels of the drug were much lower than its plasma levels

Originator

Curator's Comment:: By 1981, Cherry L. Herald, a scientist working in Pettit’s lab, had isolated the first milligram of what would be known as bryostatin 1 from that California collection of B. neritina

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
92.94 ng/mL
40 μg/kg single, intravenous
dose: 40 μg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BRYOSTATIN 1 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
376.7 ng × h/mL
40 μg/kg single, intravenous
dose: 40 μg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BRYOSTATIN 1 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
22.96 h
40 μg/kg single, intravenous
dose: 40 μg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
BRYOSTATIN 1 plasma
Mus musculus
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
PubMed

PubMed

TitleDatePubMed
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.
1996 Oct 10
Bryostatin 1 enhances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-xL.
1999 Oct
Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.
2000 Mar
Induction of cIAP-2 in human colon cancer cells through PKC delta/NF-kappa B.
2003 Dec 19
Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells.
2004 Mar 30
Effect of serum and antioxidants on the immunogenicity of protein kinase C-activated chronic lymphocytic leukemia cells.
2005 Jan-Feb
Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.
2015 Jan 5
Patents

Patents

Sample Use Guides

The maximum tolerated dose of bryostatin-1 in humans has been found to be about 25 ug/m2/week, given intravenously over up to 8 weeks
Route of Administration: Intravenous
In Vitro Use Guide
Preincubation of T-cell- and adherent cell-depleted bone marrow mononuclear cells with 12.5 nM bryostatin 1 and either 1.25 or 50 ng/ml recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) for 24 h resulted in an 18%-30% survival at 4-5 Gy, whereas cells exposed to rGM-CSF alone gave rise to no detectable colonies at radiation doses greater than 2.5 Gy. Coadministration of bryostatin 1 also led to a threefold increase in Do values for both rGM-CSF concentrations. A similar enhancement of radioprotective effects was observed with the tumor-promoting phorbol ester phorbol dibutyrate. Exposure of cells to both bryostatin 1 and rGM-CSF immediately the following irradiation also resulted in enhanced progenitor cell survival when compared to rGM-CSF alone, but radioprotective effects were less than those observed when cells were preincubated with these factors. It was suggested, that bryostatin 1 potentiated the in vitro radioprotective effects of rGM-CSF and might also regulate the lineage specificity of this response.
Substance Class Chemical
Created
by admin
on Sat Jun 26 08:10:19 UTC 2021
Edited
by admin
on Sat Jun 26 08:10:19 UTC 2021
Record UNII
37O2X55Y9E
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
BRYOSTATIN 1
MI   WHO-DD  
Common Name English
BRYOSTATIN 1 [WHO-DD]
Common Name English
2,4-OCTADIENOIC ACID, (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(21.3.1.13,7.111,15)NONACOS
Systematic Name English
NSC-339555
Code English
BRYOSTATIN-1
Common Name English
BRYOSTATIN 1 [MI]
Common Name English
Classification Tree Code System Code
FDA ORPHAN DRUG 148201
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
NCI_THESAURUS C2089
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
EU-Orphan Drug EU/3/02/099
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
FDA ORPHAN DRUG 471415
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C1026
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
FDA UNII
37O2X55Y9E
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
EPA CompTox
83314-01-6
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
PUBCHEM
5280757
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
CAS
83314-01-6
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
MERCK INDEX
M2736
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY Merck Index
MESH
C046785
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
DRUG BANK
DB11752
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
EVMPD
SUB13129MIG
Created by admin on Sat Jun 26 08:10:19 UTC 2021 , Edited by admin on Sat Jun 26 08:10:19 UTC 2021
PRIMARY
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