INDIBULIN

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H16ClN3O2
Molecular Weight	389.834
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=CC=C(CN2C=C(C(=O)C(=O)NC3=CC=NC=C3)C4=CC=CC=C24)C=C1

InChI

InChIKey=SOLIIYNRSAWTSQ-UHFFFAOYSA-N

InChI=1S/C22H16ClN3O2/c23-16-7-5-15(6-8-16)13-26-14-19(18-3-1-2-4-20(18)26)21(27)22(28)25-17-9-11-24-12-10-17/h1-12,14H,13H2,(H,24,25,28)

HIDE SMILES / InChI

Molecular Formula	C22H16ClN3O2
Molecular Weight	389.834
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=587341 | http://adisinsight.springer.com/drugs/800011203 | https://www.ncbi.nlm.nih.gov/pubmed/11196193 | https://www.ncbi.nlm.nih.gov/pubmed/15703812 | https://www.ncbi.nlm.nih.gov/pubmed/19404582

Indibulin is a novel synthetic compound that was identified in a cell-based screening assay to discover cytotoxic drugs. Indibulin destabilizes microtubules and blocks cell cycle transition specifically at the G2-M phase. Indibulin effectively induces apoptosis through Bcl-2 phosphorylation and Bax translocation in human malignant glioma cells in a p53-independent manner. This agent has been shown to be active against multidrug-resistant (MDR) and taxane-resistant tumour cell lines. Indibulin was used in phase I/II clinical trials of patients with advanced solid tumours (metastatic breast cancer). Pharmacokinetic analysis showed a better tolerability underfeeding condition. Dose-limiting toxicities were nausea and vomiting, which seemed to be related to solvent lactic acid.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Tubulin 69 Target ID: CHEMBL2111464 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11196193	Inhibitor 8504
G2/M transition of mitotic cell cycle 2 Target ID: GO:0000086 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11196193	Blocker 555	0.036 µM [IC50]
Apoptosis 156 Target ID: map04210 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15703812	Activator 1447

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 432 Sources: https://clinicaltrials.gov/ct2/show/NCT01113970 http://adisinsight.springer.com/drugs/800011203	Primary		Phase II 1147	Unknown Approved Use Unknown
Solid tumors 147 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19404582 https://www.ncbi.nlm.nih.gov/pubmed/17146730	Primary		Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
280 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19404582	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		INDIBULIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
95 ng/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19404582	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		INDIBULIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
1253 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19404582	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		INDIBULIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
597 ng × h/mL EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19404582	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		INDIBULIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
23 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19404582	250 mg single, oral dose: 250 mg route of administration: Oral experiment type: SINGLE co-administered:		INDIBULIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
24 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/19404582	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		INDIBULIN plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Doses

Dose	Population	Adverse events
600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	Other AEs: Nausea, Vomiting... Other AEs: Nausea (grade 1, 3 patients) Vomiting (grade 1, 3 patients) Fatigue (grade 2, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17146730/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17146730/	DLT: vomiting, Nausea... Dose limiting toxicities: vomiting (2 patients) Nausea (grades 1-2, 2 patients) Sources: https://pubmed.ncbi.nlm.nih.gov/17146730/
100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	DLT: elevated AST levels, elevated ALT levels... Dose limiting toxicities: elevated AST levels (grade 3, 1 pt) elevated ALT levels (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	DLT: fatigue... Dose limiting toxicities: fatigue (grade 3, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
250 mg 1 times / day multiple, oral Studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	DLT: increased AP, Gamma glutamyl transpeptidase increased... Dose limiting toxicities: increased AP (grade 3, 1 pt) Gamma glutamyl transpeptidase increased (grade 4, 1 pt) Sources: https://pubmed.ncbi.nlm.nih.gov/19404582

AEs

AE	Significance	Dose	Population
Nausea	grade 1, 3 patients	600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
Vomiting	grade 1, 3 patients	600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
Fatigue	grade 2, 1 pt	600 mg 2 times / day multiple, oral Highest studied dose Dose: 600 mg, 2 times / day Route: oral Route: multiple Dose: 600 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
vomiting	2 patients DLT, Disc. AE	80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17146730/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17146730/
Nausea	grades 1-2, 2 patients DLT	80 mg 1 times / day multiple, oral Highest studied dose Dose: 80 mg, 1 times / day Route: oral Route: multiple Dose: 80 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17146730/	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17146730/
elevated ALT levels	grade 3, 1 pt DLT, Disc. AE	100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
elevated AST levels	grade 3, 1 pt DLT, Disc. AE	100 mg 1 times / day multiple, oral Studied dose Dose: 100 mg, 1 times / day Route: oral Route: multiple Dose: 100 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
fatigue	grade 3, 1 pt DLT	150 mg 1 times / day multiple, oral Studied dose Dose: 150 mg, 1 times / day Route: oral Route: multiple Dose: 150 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FASTED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
increased AP	grade 3, 1 pt DLT	250 mg 1 times / day multiple, oral Studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582
Gamma glutamyl transpeptidase increased	grade 4, 1 pt DLT	250 mg 1 times / day multiple, oral Studied dose Dose: 250 mg, 1 times / day Route: oral Route: multiple Dose: 250 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/19404582	unhealthy Health Status: unhealthy Sex: M+F Food Status: FED Sources: https://pubmed.ncbi.nlm.nih.gov/19404582

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	MRP 9 P-gp 2052

Drug as perpetrator

Target	Modality	Activity
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=174007308	no
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=174007308	yes [IC50 0.0332 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=174007308	yes [IC50 0.1068 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=174007308	yes [IC50 0.3011 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
MRP 9	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11196193/	no
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11196193/	no

Sourcing

Vendor/Aggregator	ID	URL
AChemBlock	10069	http://www.achemblock.com/catalogsearch/result/?q=10069
Angene	AGN-PC-0WHDN4	http://www.angenechemical.com/productshow/AGN-PC-0WHDN4.html
BLD Pharm	BD251733	http://www.bldpharm.com/search/Search.html?keyword=BD251733
BOC Sciences	204205-90-3	http://www.bocsci.com/description.asp?cas=204205-90-3
Chem Scene	CS-0007536	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0007536
ChemDiv	BB54-1721	http://chemistryondemand.com:8080/eShop/search_results.jsp?idnumber=BB54-1721
eMolecules	1986394	https://orderbb.emolecules.com/search/#?query=1986394
eNovation Chemicals	D500720	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D500720&searchbtn.x=0&searchbtn.y=0
Hairui	HR146237	http://www.hairuichem.com/en/product/search.do?q=HR146237
Lab Network	LN00334066	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00334066
Lab Seeker	SC-84469	http://www.labseeker.com/search.php?keywords=SC-84469&category=0
mcule	MCULE-2626264660	https://mcule.com/MCULE-2626264660/
MedChem Express	HY-13649	https://www.medchemexpress.com/search.html?q=HY-13649&ft=&fa=&fp=
MolPort	MolPort-002-739-496	https://www.molport.com/shop/molecule-link/MolPort-002-739-496
MuseChem	I007312	https://www.musechem.com/product/I007312.html
Princeton BioMolecular Research	OSSL_660408	http://www.princetonbio.com/order_online?common_id=OSSL_660408
Princeton BioMolecular Research	PBMR221836	http://www.princetonbio.com/order_online?common_id=PBMR221836
TimTec	SBB013544	http://www.echemstore.com/catalogsearch/result/?q=SBB013544
TimTec	ST099617	http://www.echemstore.com/catalogsearch/result/?q=ST099617
Tocris	3728	https://www.tocris.com/search.php?Type=QuickSearch&Value=3728
Toronto Research Chemicals	I533753	https://www.trc-canada.com/product-detail/?CatNum=I533753
Toronto Research Chemicals	L486208	https://www.trc-canada.com/product-detail/?CatNum=L486208
Wonderchem	WD05K0U	http://www.wonder-chem.com/search.html?text=WD05K0U

PubMed

Title	Date	PubMed
Gateways to clinical trials.	2010-12	21225012
Gateways to clinical trials.	2010-04-13	20383346
Dose-finding and pharmacokinetic study of orally administered indibulin (D-24851) to patients with advanced solid tumors.	2010-04	19404582
Indibulin, a novel microtubule inhibitor, discriminates between mature neuronal and nonneuronal tubulin.	2009-01-01	19118000
Side chain modifications of (indol-3-yl)glyoxamides as antitumor agents.	2008-10	18821257
Design, synthesis and cytotoxicity of novel podophyllotoxin derivatives.	2008-06	18520089
In vivo evaluation of indolyl glyoxamides in the phenotypic sea urchin embryo assay.	2007-12	17991295
Phase I dose-finding and pharmacokinetic trial of orally administered indibulin (D-24851) to patients with solid tumors.	2007-06	17146730
Antirestenotic effects of a novel polymer-coated d-24851 eluting stent. Experimental data in a rabbit iliac artery model.	2006-06-30	17828426
Microtubule inhibitor D-24851 induces p53-independent apoptotic cell death in malignant glioma cells through Bcl-2 phosphorylation and Bax translocation.	2005-03	15703812
Stable isotopically labeled internal standards in quantitative bioanalysis using liquid chromatography/mass spectrometry: necessity or not?	2005	15645520
Quantitative analysis of D-24851, a novel anticancer agent, in human plasma and urine by liquid chromatography coupled with tandem mass spectrometry.	2004	15216507
Differential roles of p21(Waf1) and p27(Kip1) in modulating chemosensitivity and their possible application in drug discovery studies.	2001-11	11641417
D-24851, a novel synthetic microtubule inhibitor, exerts curative antitumoral activity in vivo, shows efficacy toward multidrug-resistant tumor cells, and lacks neurotoxicity.	2001-01-01	11196193

Patents

Sample Use Guides

In Vivo Use Guide

100 mg, 150 mg, 250 mg, 350 mg and 600 mg once daily (QD), 450 mg and 600 mg twice daily (BID). After a washout period, patients received indibulin at the pre-defined daily dose for 14 days every 3 weeks (multiple dose part).

Route of Administration: Oral

In Vitro Use Guide

To examine the cytotoxic effects of indibulin on malignant glioma cells, the four human glioma cell lines, which have different p53 status (U373-MG and T98G have mutated p53, and U87-MG and D54 have wild-type p53), were treated with different concentrations of indibulin for 2 days. The viability of all cell lines was reduced in a dose-dependent manner. The IC50s for indibulin in U373-MG, T98G, U87-MG, and D54 cells were 150, 180, 120, and 190 nM, respectively.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:30:20 GMT 2025` Edited by `admin` on `Mon Mar 31 18:30:20 GMT 2025`
Record UNII	80K4H2RB8P
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

INDIBULIN

Official Name

English

D-24851

Preferred Name

English

ZIO-301

Code

English

2-{1-[(4-Chlorophenyl)methyl]-1H-indol-3-yl}-2-oxo-N-(pyridin-4-yl)acetamide

Systematic Name

English

indibulin [INN]

Common Name

English

INDIBULIN [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C25974