BRYOSTATIN 1

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C47H68O17
Molecular Weight	905.0326
Optical Activity	UNSPECIFIED
Defined Stereocenters	11 / 11
E/Z Centers	4
Charge	0

SHOW SMILES / InChI

Structure Search

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@]4(O)O[C@@]([H])(C\C(=C/C(=O)OC)[C@@H]4OC(=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

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	905.0326
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	11 / 11
E/Z Centers	4
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16834754 | https://www.ncbi.nlm.nih.gov/pubmed/8631017

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Protein kinase C, PKC; classical/novel 4 Target ID: CHEMBL2096620 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16834754	Agonist 2678

Conditions

Condition	Modality	Highest Phase	Product
Head and neck cancer 50 Sources: https://clinicaltrials.gov/ct2/show/NCT00003443	Primary	Phase II 1132	Unknown Approved Use Unknown
Ovarian cancer 157 Sources: https://clinicaltrials.gov/ct2/show/NCT00004008	Primary	Phase II 1132	Unknown Approved Use Unknown
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT00003936	Primary	Phase II 1132	Unknown Approved Use Unknown
Myelodysplastic syndromes 58 Sources: https://clinicaltrials.gov/ct2/show/NCT00003171	Primary	Phase II 1132	Unknown Approved Use Unknown
Leukemia 87 Sources: https://clinicaltrials.gov/ct2/show/NCT00003171	Primary	Phase II 1132	Unknown Approved Use Unknown
Alzheimer’s disease 272 Sources: https://clinicaltrials.gov/ct2/show/NCT02431468	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
92.94 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8631017	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

Value	Dose	Co-administered	Analyte	Population
376.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8631017	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
22.96 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8631017	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

Sourcing

Vendor/Aggregator	ID	URL
Apollo Scientific	BIB0342	http://www.apolloscientific.co.uk/chemical_results.php?qstext=BIB0342&product_group=%25&search_fieldname=header_search
BOC Sciences	83314-01-6	http://www.bocsci.com/description.asp?cas=83314-01-6
Ryan Scientific	107-57914	https://ryansci.com/products?q=107-57914&list_q=&search_type=exact

PubMed

Title	Date	PubMed
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	8892972
Bryostatin 1 enhances paclitaxel-induced mitochondrial dysfunction and apoptosis in human leukemia cells (U937) ectopically expressing Bcl-xL.	1999 Oct	10516758
Phase II trial of bryostatin 1 in patients with relapsed low-grade non-Hodgkin's lymphoma and chronic lymphocytic leukemia.	2000 Mar	10741703
Induction of cIAP-2 in human colon cancer cells through PKC delta/NF-kappa B.	2003 Dec 19	14527959
Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells.	2004 Mar 30	15070760
Effect of serum and antioxidants on the immunogenicity of protein kinase C-activated chronic lymphocytic leukemia cells.	2005 Jan-Feb	15614042
Elucidating mechanisms of toxicity using phenotypic data from primary human cell systems--a chemical biology approach for thrombosis-related side effects.	2015 Jan 5	25569083

Patents

Sample Use Guides

In Vivo Use Guide

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 `Fri Dec 15 15:54:43 UTC 2023` Edited by `admin` on `Fri Dec 15 15:54:43 UTC 2023`
Record UNII	37O2X55Y9E
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

BRYOSTATIN 1

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

Bryostatin 1 [WHO-DD]

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

148201