TALTOBULIN

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H43N3O4
Molecular Weight	473.648
Optical Activity	UNSPECIFIED
Defined Stereocenters	3 / 3
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN[C@H](C(=O)N[C@H](C(=O)N(C)[C@H](\C=C(/C)C(O)=O)C(C)C)C(C)(C)C)C(C)(C)C1=CC=CC=C1

InChI

InChIKey=CNTMOLDWXSVYKD-PSRNMDMQSA-N

InChI=1S/C27H43N3O4/c1-17(2)20(16-18(3)25(33)34)30(10)24(32)22(26(4,5)6)29-23(31)21(28-9)27(7,8)19-14-12-11-13-15-19/h11-17,20-22,28H,1-10H3,(H,29,31)(H,33,34)/b18-16+/t20-,21-,22-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/18316576
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/18240145

Taltobulin, also known as HTI-286 and SPA-110, is a fully synthetic analog of the natural tripeptide hemiasterlin, inhibits tubulin polymerization and circumvents transport-based resistance to taxanes. Taltobulin was a potent inhibitor of proliferation (mean IC50 = 4 nm in 18 human tumor cell lines) and had substantially less interaction with multidrug resistance protein (P-glycoprotein) than currently used antimicrotubule agents, including paclitaxel, docetaxel, vinorelbine, or vinblastine. Taltobulin showed strong antitumor activity both in androgen-dependent and androgen- independent tumors and may be a promising agent in second- line treatment strategies for patients suffering from docetaxel- refractory prostate cancer.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
UMUC3 1 Target ID: CHEMBL612799 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18316576	Inhibitor 8297	2.0 nM [IC50]
transformed cell apoptotic process 108 Target ID: GO:0006927 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18240145	Activator 1430
Tubulin 69 Target ID: CHEMBL2095182 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15865430	Modulator 828	0.3 µM [Kd]
Tubulin polymerisation 1 Target ID: Tubulin polymerisation Sources: https://www.ncbi.nlm.nih.gov/pubmed/15865430	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: http://adisinsight.springer.com/drugs/800019128	Primary		Phase I 428	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461		BCRP 75 MRP1 48 MRP3 53 P-gp 257

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680351	inconclusive [IC50 33.7858 uM]
BCRP 773	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15486199/	no
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363680351	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363680351	no
MRP1 172	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15486199/	no
MRP3 207	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15486199/	no
P-gp 1650	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/15486199/	no
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363680351	yes [IC50 0.0184 uM]

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00BFLI	https://www.1pchem.com/search?query=1P00BFLI
1PlusChem LLC	1P00BFN7	https://www.1pchem.com/search?query=1P00BFN7
AK Scientific	4082AH	https://aksci.com/item_detail.php?cat=4082AH
AlchemyPharm	AP00510	https://www.alchemypharm.com/pharm/search.do?q=AP00510
Axon MedChem	1650	https://www.axonmedchem.com/product/1650
BLD Pharm	BD630569	http://www.bldpharm.com/search/Search.html?keyword=BD630569
BLD Pharm	BD630570	http://www.bldpharm.com/search/Search.html?keyword=BD630570
BOC Sciences	228266-40-8	http://www.bocsci.com/description.asp?cas=228266-40-8
Chem Scene	CS-3299	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3299
Chem Scene	CS-3787	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3787
Chem Scene	CS-5091	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5091
Lab Seeker	SC-82887	http://www.labseeker.com/search.php?keywords=SC-82887&category=0
MedChem Express	HY-15584A	https://www.medchemexpress.com/search.html?q=HY-15584A&ft=&fa=&fp=
MedChem Express	HY-15584	https://www.medchemexpress.com/search.html?q=HY-15584B&ft=&fa=&fp=
MedChem Express	HY-15584B	https://www.medchemexpress.com/search.html?q=HY-15584B&ft=&fa=&fp=
MolPort	MolPort-039-139-820	https://www.molport.com/shop/molecule-link/MolPort-039-139-820
MolPort	MolPort-046-417-075	https://www.molport.com/shop/molecule-link/MolPort-046-417-075
MolPort	MolPort-046-418-221	https://www.molport.com/shop/molecule-link/MolPort-046-418-221
eMolecules	275094706	https://orderbb.emolecules.com/search/#?query=275094706
eMolecules	275132101	https://orderbb.emolecules.com/search/#?query=275132101
eMolecules	44848345	https://orderbb.emolecules.com/search/#?query=44848345
eMolecules	50550725	https://orderbb.emolecules.com/search/#?query=50550725
eMolecules	72972971	https://orderbb.emolecules.com/search/#?query=72972971
mcule	MCULE-4366806420	https://mcule.com/MCULE-4366806420/
mcule	MCULE-7319582372	https://mcule.com/MCULE-7319582372/
mcule	MCULE-8054198749	https://mcule.com/MCULE-8054198749/
mcule	MCULE-9642029370	https://mcule.com/MCULE-9642029370/

PubMed

Title	Date	PubMed
		252160333
Cells resistant to HTI-286 do not overexpress P-glycoprotein but have reduced drug accumulation and a point mutation in alpha-tubulin.	2004 Oct	15486199

Patents

Sample Use Guides

In Vivo Use Guide

low dose (0.01 mg/mL), or high dose (0.05-0.125 mg/mL) Taltobulin prepared in PBS, intravesical treatment

Route of Administration: Other

In Vitro Use Guide

Taltobulin was a potent inhibitor of proliferation in all tested bladder cancer cell lines at low nanomolar concentrations. The mean IC50 combining all cell lines was 4.0 +/- 2.1 nmol/L.

Name

Type

Language

TALTOBULIN

Official Name

English

L-VALINAMIDE,N,.BETA.,.BETA.-TRIMETHYL-L-PHENYLALANINE-N-((1S,2E)-3-CARBOXY-1-(1-METHYLETHYL)-2-BUTENYL)-N,3-DIMETHYL

Common Name

English

(4S)-4-[[(2S)-3,3-Dimethyl-2-[[(2S)-3-methyl-2-(methylamino)-3-phenylbutanoyl]amino]butanoyl]methylamino]-2,5-dimethylhex-2-enoic acid

Systematic Name

English

HTI-286

Code

English

TALTOBULIN [USAN]

Common Name

English

taltobulin [INN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67421