DOLASTATIN 10

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C42H68N6O6S
Molecular Weight	785.091
Optical Activity	UNSPECIFIED
Defined Stereocenters	9 / 9
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CCCN1C(=O)C[C@@H](OC)[C@H]([C@@H](C)CC)N(C)C(=O)[C@@H](NC(=O)[C@H](C(C)C)N(C)C)C(C)C)[C@H](OC)[C@@H](C)C(=O)N[C@@H](CC2=CC=CC=C2)C3=NC=CS3

InChI

InChIKey=OFDNQWIFNXBECV-VFSYNPLYSA-N

InChI=1S/C42H68N6O6S/c1-13-28(6)37(47(10)42(52)35(26(2)3)45-40(51)36(27(4)5)46(8)9)33(53-11)25-34(49)48-22-17-20-32(48)38(54-12)29(7)39(50)44-31(41-43-21-23-55-41)24-30-18-15-14-16-19-30/h14-16,18-19,21,23,26-29,31-33,35-38H,13,17,20,22,24-25H2,1-12H3,(H,44,50)(H,45,51)/t28-,29+,31-,32-,33+,35-,36-,37-,38+/m0/s1

HIDE SMILES / InChI

Molecular Formula	C42H68N6O6S
Molecular Weight	785.091
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	9 / 9
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16133801 | https://clinicaltrials.gov/ct2/show/NCT00005579 | https://www.ncbi.nlm.nih.gov/pubmed/11106233

Dolastatin 10 is an unusual peptide of marine origin which binds to tubulin, inhibits microtubule assembly, resulting in the formation of tubulin aggregates and inhibition of mitosis. Dolastatin 10 has been used in trials phase II studying the treatment of Sarcoma, Leukemia, Lymphoma, Liver Cancer, among others. In case of hormone-refractory prostate cancer, it lacks significant clinical activity as a single agent and also dolastatin-10 is inactive against hepatobiliary and pancreatic carcinomas.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1540211	Binding Agent 1064

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 97 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16133801	Primary	Phase II 1132	Unknown Approved Use Unknown
Kidney cancer 10 Sources: https://clinicaltrials.gov/ct2/show/NCT00003914	Primary	Phase II 1132	Unknown Approved Use Unknown
Hormone-refractory prostate cancer 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11106233	Primary	Phase II 1132	Unknown Approved Use Unknown
Chronic lymphocytic leukemia 59 Sources: https://clinicaltrials.gov/ct2/show/NCT00005579	Primary	Phase II 1132	Unknown Approved Use Unknown
Lymphoma 58 Sources: https://clinicaltrials.gov/ct2/show/NCT00005579	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
57.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	65 μg/m² single, intravenous dose: 65 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
55 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	100 μg/m² single, intravenous dose: 100 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
143.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	200 μg/m² single, intravenous dose: 200 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
96 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	300 μg/m² single, intravenous dose: 300 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
14.96 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	65 μg/m² single, intravenous dose: 65 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
19.7 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	100 μg/m² single, intravenous dose: 100 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
52.49 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	200 μg/m² single, intravenous dose: 200 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
89.9 ng × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	300 μg/m² single, intravenous dose: 300 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
0.09 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	65 μg/m² single, intravenous dose: 65 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.13 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	100 μg/m² single, intravenous dose: 100 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.12 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	200 μg/m² single, intravenous dose: 200 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
0.06 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10778954	300 μg/m² single, intravenous dose: 300 μg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	DOLASTATIN 10 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY34330	https://www.001chemical.com/chem/search?q=DY34330
ApexBio Technology	B1066	https://www.apexbt.com/catalogsearch/result/?q=B1066
BOC Sciences	110417-88-4	http://www.bocsci.com/description.asp?cas=110417-88-4
Chem Scene	CS-1825	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-1825
MedChem Express	HY-15580	https://www.medchemexpress.com/search.html?q=HY-15580&ft=&fa=&fp=
MolPort	MolPort-042-694-775	https://www.molport.com/shop/molecule-link/MolPort-042-694-775
MolPort	MolPort-046-417-071	https://www.molport.com/shop/molecule-link/MolPort-046-417-071
Molcore	MC34330	http://www.molcore.com/CatMC34330.html
PI Chemicals	PI-37007	http://www.pipharm.com/catalog_products/PI-37007.html
Tocris	3375	https://www.tocris.com/search.php?Type=QuickSearch&Value=3375
eMolecules	50282705	https://orderbb.emolecules.com/search/#?query=50282705
eNovation Chemicals	D548550	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D548550&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-4504589414	https://mcule.com/MCULE-4504589414/
mcule	MCULE-4663805198	https://mcule.com/MCULE-4663805198/

PubMed

Title	Date	PubMed
Interaction of dolastatin 10 with bovine brain tubulin.	1992 Feb 4	1540211
Phase II study of dolastatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma.	2000 Nov	11106233
Phase II trials of dolastatin-10 in advanced pancreaticobiliary cancers.	2005 Oct	16133801

Patents

Sample Use Guides

In Vivo Use Guide

advanced pancreaticobiliary cancers: dolastatin-10 400 microg/m(2) was administered intravenously by bolus every 21 days. Restaging CT scans were obtained every 2 cycles metastatic prostate adenocarcinoma: dolastatin-10 was administered at a dose of 400 microg/m2 i.v. every 3 weeks. Dose escalation to 450 microg/m2 was permitted.

Route of Administration: Intravenous

In Vitro Use Guide

Dolastatin 10 had growth inhibitory activity against four small-cell lung cancer (SCLC) cell lines (NCI-H69, -H82, -H446, -H510) with IC50 values ranging from 0.032 to 0.184 nM. All four cell lines exhibited evidence of apoptosis after 48 h of exposure to 1.3 nM dolastatin 10. Immunoblot analysis revealed that 1.3 nM dolastatin 10 altered the electrophoretic mobility of bcl-2 in NCI-H69 and -H510 cells within 16 h of treatment. Incubation of protein extract from dolastatin 10-treated NCI-H69 and -H510 cells with calcineurin resulted in the disappearance of the altered mobility species, suggesting dolastatin 10-induced bcl-2 phosphorylation.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:53:30 GMT 2023` Edited by `admin` on `Fri Dec 15 15:53:30 GMT 2023`
Record UNII	EI946JT51X
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

DOLASTATIN 10

Common Name

English

DLS 10

Common Name

English

L-VALINAMIDE, N,N-DIMETHYL-L-VALYL-N-((1S,2R)-2-METHOXY-4-((2S)-2-((1R,2R)-1-METHOXY-2-METHYL-3-OXO-3-(((1S)-2-PHENYL-1-(2-THIAZOLYL)ETHYL)AMINO)PROPYL)-1-PYRROLIDINYL)-1-((1S)-1-METHYLPROPYL)-4-OXOBUTYL)-N-METHYL-

Common Name

English

NSC-376128

Code

English

N,N-DIMETHYL-VAL-N-(2-METHOXY-4-(2-(1-METHOXY-2-METHYL-3-OXO-3-((2-PHENYL-1-(2-THIAZOLYL)ETHYL)AMINO)PROPYL)-1-PYRROLIDINYL)-1-(1-METHYLPROPYL)-4-OXOBUTYL)-N-METHYL-VALINAMIDE (2S-(1(1R*(R*),2S*),2R*(1S*,2S*,3(R*))))

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1893