SB-743921

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C31H33ClN2O3
Molecular Weight	517.058
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)[C@@H](N(CCCN)C(=O)C1=CC=C(C)C=C1)C2=C(CC3=CC=CC=C3)C(=O)C4=C(O2)C=C(Cl)C=C4

InChI

InChIKey=PGXYIBJJCLWJST-MUUNZHRXSA-N

InChI=1S/C31H33ClN2O3/c1-20(2)28(34(17-7-16-33)31(36)23-12-10-21(3)11-13-23)30-26(18-22-8-5-4-6-9-22)29(35)25-15-14-24(32)19-27(25)37-30/h4-6,8-15,19-20,28H,7,16-18,33H2,1-3H3/t28-/m1/s1

HIDE SMILES / InChI

Molecular Formula	C31H33ClN2O3
Molecular Weight	517.058
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25860245
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23875972 | https://clinicaltrials.gov/ct2/show/NCT00136513 | https://www.ncbi.nlm.nih.gov/pubmed/20461380

SB-743921 is a synthetic small molecule with potential antineoplastic properties. SB-743921 selectively inhibits the ATP-binding domain of the kinesin spindle protein (KSP), an important protein involved in the early stages of mitosis that is expressed in proliferating cells. Inhibition of KSP results in inhibition of mitotic spindle assembly and interrupts cell division, thereby causing cell cycle arrest and induction of apoptosis. SB-743921 has greater than 40,000 fold selectivity for KSP over other kinesins. SB-743921 has demonstrated promising anti-cancer activity in a variety of in vivo and in vitro human cancer models in preclinical studies. Furthermore, anti-cancer effect has been demonstrated in taxane-refractory malignancies with SB-743921. Toxicity studies demonstrated predictable neutropenias and gastrointestinal toxicities without clear evidence of neurotoxicity. The recommended phase II dose for SB-743921 as a 1-h infusion every 21 days is 4 mg/m2.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Kinesin-like protein 1 12 Target ID: CHEMBL4581 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23875972	Inhibitor 8504		0.14 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Large B-cell lymphoma 3 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25860245	Primary	Preclinical	Unknown Approved Use Unknown
Solid tumors 147 Sources: https://clinicaltrials.gov/ct2/show/NCT00136513	Primary	Phase I 438	Unknown Approved Use Unknown
Non-Hodgkin's lymphoma 81 Sources: https://clinicaltrials.gov/ct2/show/NCT00343564	Primary	Phase II 1147	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
233 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	2 mg/m² single, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
489 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	4 mg/m² single, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
607 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	5 mg/m² single, intravenous dose: 5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
817 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	6 mg/m² single, intravenous dose: 6 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
803 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	8 mg/m² single, intravenous dose: 8 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
1706 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	2 mg/m² single, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3776 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	4 mg/m² single, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3776 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	5 mg/m² single, intravenous dose: 5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3776 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	6 mg/m² single, intravenous dose: 6 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
3776 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	8 mg/m² single, intravenous dose: 8 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
31.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	2 mg/m² single, intravenous dose: 2 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
28 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	4 mg/m² single, intravenous dose: 4 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
36.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	5 mg/m² single, intravenous dose: 5 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
33.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	6 mg/m² single, intravenous dose: 6 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
30.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/20461380/	8 mg/m² single, intravenous dose: 8 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	SB743921 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
10 mg/m2 1 times / 2 weeks multiple, intravenous Highest studied dose Dose: 10 mg/m2, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 10 mg/m2, 1 times / 2 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/	DLT: Thrombocytopenia, Dehydration... Other AEs: Neutropenia, Fatigue... Dose limiting toxicities: Thrombocytopenia (grade 3-4, 57%) Dehydration (grade 3, 14%) Other AEs: Neutropenia (grade 3-4, 57%) Fatigue (grade 1-2, 57%) Leucopenia (grade 3-4, 14%) Nausea (grade 1-2, 14%) Anemia (grade 3-4, 29%) Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/
4 mg/m2 1 times / 3 weeks multiple, intravenous MTD Dose: 4 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 4 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	DLT: Hypophosphatemia, Pulmonary embolism... Dose limiting toxicities: Hypophosphatemia (grade 3, 3.7%) Pulmonary embolism (grade 5, 3.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/
6 mg/m2 1 times / 2 weeks multiple, intravenous MTD Dose: 6 mg/m2, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 6 mg/m2, 1 times / 2 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/	DLT: Sepsis... Other AEs: Neutropenia, Thrombocytopenia... Dose limiting toxicities: Sepsis (grade 4, 10%) Other AEs: Neutropenia (grade 3-4, 40%) Thrombocytopenia (grade 1-2, 10%) Fatigue (grade 1-2, 10%) Pyrexia (grade 1-2, 10%) Dyspnea (grade 1-2, 10%) Leucopenia (grade 3-4, 20%) Nausea (grade 1-2, 30%) Anemia (grade 1-2, 40%) Cough (grade 1-2, 10%) Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/
9 mg/m2 1 times / 2 weeks multiple, intravenous MTD Dose: 9 mg/m2, 1 times / 2 weeks Route: intravenous Route: multiple Dose: 9 mg/m2, 1 times / 2 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/	DLT: Neutropenia... Other AEs: Thrombocytopenia, Fatigue... Dose limiting toxicities: Neutropenia (grade 3-4, 57%) Other AEs: Thrombocytopenia (grade 1-4, 29%) Fatigue (grade 1-2, 14%) Pyrexia (grade 1-2, 29%) Leucopenia (grade 1-2, 29%) Nausea (grade 1-2, 29%) Anemia (grade 3-4, 14%) Diarrhea (grade 1-2, 14%) Sources: https://pubmed.ncbi.nlm.nih.gov/25665464/
5 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 5 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 5 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	DLT: Febrile neutropenia... Dose limiting toxicities: Febrile neutropenia (grade 4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/
6 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 6 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 6 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	DLT: Neutropenia, Hyponatremia... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Hyponatremia (grade 3, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/
8 mg/m2 1 times / 3 weeks multiple, intravenous Studied dose Dose: 8 mg/m2, 1 times / 3 weeks Route: intravenous Route: multiple Dose: 8 mg/m2, 1 times / 3 weeks Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/	DLT: Neutropenia, Transaminase elevation... Dose limiting toxicities: Neutropenia (grade 4, 33.3%) Transaminase elevation (grade 3-4, 33.3%) Sources: https://pubmed.ncbi.nlm.nih.gov/20461380/

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP2C19 2057 CYP1A2 2153

Drug as perpetrator

Target	Modality	Activity
CYP1A2 2333	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzU2IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIzMjU0MjkifX0=	no [IC50 >25 uM]
CYP2C19 2141	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNjIyIiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIzMjU0MjkifX0=	no [IC50 >25 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzMzk3IiwidXNlX2N1c3RvbV9xdWVyeSI6dHJ1ZSwic2VhcmNoX3Rlcm0iOiIiLCJ0ZXh0X2ZpbHRlciI6IkNIRU1CTDIzMjU0MjkifX0=	no [IC50 >25 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyODkiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjMyNTQyOSJ9fQ==	no [IC50 >25 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwzNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjMyNTQyOSJ9fQ==	yes [IC50 4 uM]

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://www.ebi.ac.uk/chembl/g/#browse/activities/full_state/eyJsaXN0Ijp7InNldHRpbmdzX3BhdGgiOiJFU19JTkRFWEVTX05PX01BSU5fU0VBUkNILkFDVElWSVRZIiwiY3VzdG9tX3F1ZXJ5IjoidGFyZ2V0X2NoZW1ibF9pZDpDSEVNQkwyNDAiLCJ1c2VfY3VzdG9tX3F1ZXJ5Ijp0cnVlLCJzZWFyY2hfdGVybSI6IiIsInRleHRfZmlsdGVyIjoiQ0hFTUJMMjMyNTQyOSJ9fQ==

PubMed

Title	Date	PubMed
The novel kinesin spindle protein (KSP) inhibitor SB-743921 exhibits marked activity in in vivo and in vitro models of aggressive large B-cell lymphoma.	2015	25860245

Patents

Sample Use Guides

In Vivo Use Guide

The recommended phase II dose for SB-743921 as a 1-h infusion every 21 days is 4 mg/m2 .

Route of Administration: Intravenous

In Vitro Use Guide

For in vitro assays, cells were counted and resuspended at a concentration of 3 x105 cells / well in a 24-well plate. SB-743921 was diluted in IMDM medium with 10% fetal bovine serum. Concentrations of SB-743921 from 1 nM to 10 μM were used in most assays. In pulse chase experiments cells were preincubated with SB-743921 for 1 or 3 hours. The cells were then washed twice with phosphate buffer solution 1X (PBS 1X) and resuspended in IMDM medium with 10% FBS. The cells were then incubated for 24, 48, or 72 hours prior to recording luminescence.

Substance Class	Chemical Created by `admin` on `Mon Mar 31 18:16:50 GMT 2025` Edited by `admin` on `Mon Mar 31 18:16:50 GMT 2025`
Record UNII	24DSZ1VN92
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SB-743921

Code

English

SB-743921 FREE BASE

Preferred Name

English

SB 743921 [WHO-DD]

Common Name

English

BENZAMIDE, N-(3-AMINOPROPYL)-N-((1R)-1-(7-CHLORO-4-OXO-3-(PHENYLMETHYL)-4H-1-BENZOPYRAN-2-YL)-2-METHYLPROPYL)-4-METHYL-

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67440