APTO-253 HYDROCHLORIDE

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C22H14FN5.ClH
Molecular Weight	403.839
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

Cl.CC1=C(C2=NC3=C(N2)C4=CC=CN=C4C5=C3C=CC=N5)C6=C(N1)C=CC(F)=C6

InChI

InChIKey=XGEPFSYBBQZKKW-UHFFFAOYSA-N

InChI=1S/C22H14FN5.ClH/c1-11-17(15-10-12(23)6-7-16(15)26-11)22-27-20-13-4-2-8-24-18(13)19-14(21(20)28-22)5-3-9-25-19;/h2-10,26H,1H3,(H,27,28);1H

HIDE SMILES / InChI

Description
Sources: http://www.bloodjournal.org/content/124/21/4813?sso-checked=true
Curator's Comment: description was created based on several sources, including http://aptose.com/apto-253/

APTO-253 is a novel small molecule that can induce expression of the genes that code for the Krüppel-like factor 4 (KLF4) master transcription factor and for the p21 cell cycle inhibitor protein, and can inhibit expression of the c-Myc oncogene, leading to cell cycle arrest and programmed cell death (apoptosis) in human-derived solid tumor and hematologic cancer cells. A Phase 1 study with APTO-253 was completed and demonstrated modest clinical activity in patients with colon cancer, acute leukemia, myelodysplastic syndrome, hematological malignancies and non-small cell lung cancers.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Krueppel-like factor 4 2 Target ID: O43474\|\|\|Q8N717 Gene ID: 9314.0 Gene Symbol: KLF4 Target Organism: Homo sapiens (Human) Sources: http://aptose.com/apto-253/	Activator 1430
Myc proto-oncogene protein 2 Target ID: CHEMBL1250348 Sources: http://aptose.com/apto-253/	Inhibitor 8297

Conditions

Condition	Modality	Highest Phase	Product
Haematological malignancies 4 Sources: https://clinicaltrials.gov/ct2/show/NCT02267863	Primary	Phase I 428	Unknown Approved Use Unknown
Acute leukemia 31 Sources: https://clinicaltrials.gov/ct2/show/NCT02267863	Primary	Phase I 428	Unknown Approved Use Unknown
Myelodysplastic syndromes 58 Sources: https://clinicaltrials.gov/ct2/show/NCT02267863	Primary	Phase I 428	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26268924	Primary	Phase I 428	Unknown Approved Use Unknown
Colon cancer 62 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26268924	Primary	Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1190 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26268924	229 mg/m² single, intravenous dose: 229 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:		APTO-253 serum	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P00GUKN	https://www.1pchem.com/search?query=1P00GUKN
AbovChem LLC	HY-16291
BLD Pharm	BD631002	http://www.bldpharm.com/search/Search.html?keyword=BD631002
Chem Scene	CS-5226	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-5226
Lab Network	LN01345818	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN01345818
Lan Pharmatech	LQT-B11877
MedChem Express	HY-16291	https://www.medchemexpress.com/search.html?q=HY-16291&ft=&fa=&fp=
MolPort	MolPort-046-417-134	https://www.molport.com/shop/molecule-link/MolPort-046-417-134
eMolecules	72973153	https://orderbb.emolecules.com/search/#?query=72973153
mcule	MCULE-5545108520	https://mcule.com/MCULE-5545108520/

PubMed

Title	Date	PubMed
Phase 1 study of APTO-253 HCl, an inducer of KLF4, in patients with advanced or metastatic solid tumors.	2015 Oct	26268924

Patents

Sample Use Guides

In Vivo Use Guide

APTO-253 HCl will be given in ascending doses starting from 20 mg/m2 until the maximum administered dose or appropriate dose is reached. Patients will be treated on APTO-253 HCl for at least 1 cycle (28 days) for safety evaluation.

Route of Administration: Intravenous

In Vitro Use Guide

APTO-253 showed potent antiproliferative activity in vitro against a panel of blood cancer cell lines, with ηM IC50 values in acute myelogenous leukemia (6.9 - 305 ηM), acute lymphoblastic leukemia and chronic myeloid leukemia (39 – 250 ηM), non-Hodgkin’s lymphoma (11 – 190 ηM) and multiple myeloma (72 – 180 ηM).

Name

Type

Language

APTO-253 HYDROCHLORIDE

Common Name

English

LOR-253 HYDROCHLORIDE

Code

English

LOR 253 HYDROCHLORIDE

Code

English

APTO-253 MONOHYDROCHLORIDE

Code

English

MTF-1 INHIBITOR APTO-253 HCL

Common Name

English

1H-IMIDAZO(4,5-F)(1,10)PHENANTHROLINE, 2-(5-FLUORO-2-METHYL-1H-INDOL-3-YL)-, HYDROCHLORIDE (1:1)

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C1742