Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C22H14FN5 |
| Molecular Weight | 367.3785 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CC1=C(C2=NC3=C(N2)C4=CC=CN=C4C5=C3C=CC=N5)C6=C(N1)C=CC(F)=C6
InChI
InChIKey=NIRXBXIPHUTNNI-UHFFFAOYSA-N
InChI=1S/C22H14FN5/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)
| Molecular Formula | C22H14FN5 |
| Molecular Weight | 367.3785 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
DescriptionCurator's Comment: description was created based on several sources, including
http://aptose.com/apto-253/
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: O43474|||Q8N717 Gene ID: 9314.0 Gene Symbol: KLF4 Target Organism: Homo sapiens (Human) Sources: http://aptose.com/apto-253/ |
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Target ID: CHEMBL1250348 Sources: http://aptose.com/apto-253/ |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
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| Primary | Unknown Approved UseUnknown |
Cmax
| 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 |
Sample Use Guides
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
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).
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 19:41:31 GMT 2023
by
admin
on
Fri Dec 15 19:41:31 GMT 2023
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| Record UNII |
WB59MRW00U
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| Record Status |
Validated (UNII)
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FDA ORPHAN DRUG |
480415
Created by
admin on Fri Dec 15 19:41:31 GMT 2023 , Edited by admin on Fri Dec 15 19:41:31 GMT 2023
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916151-99-0
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11960271
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WB59MRW00U
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ACTIVE MOIETY |
Class: Antineoplastic, Imidazole, Indole, Phenanthroline, Small molecule; Mechanism of Action: Apoptosis stimulant, GKLF protein stimulant, Proto oncogene protein c-myc inhibitor, Transcription factor MTF-1 inhibitor; Orphan Drug Status: Yes - for Acute myeloid leukaemia; Highest Development Phase: Phase I for Acute myeloid leukaemia, Haematological malignancie, Myelodysplastic syndrome, Non-small cell lung cancer, Solid tumours; Most Recent Events: 10 May 2016 Pharmacodynamic data from a preclinical study in Acute myeloid leukaemia released by Aptose Biosciences, 20 Nov 2015 The US FDA places clinical hold on a phase I trial in Haematological malignancies (Second-line therapy or greater) in USA , NCT02267863), 02 Jun 2015 APTO 253 receives Orphan Drug status for Acute myeloid leukaemia in USA
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ACTIVE MOIETY |
APTO-253 is a novel anticancer small molecule currently in a multicenter open-label, Phase I dose escalation study in patients with relapsed or refractory hematologic malignancies. APTO-253 has potent cytotoxic activity against leukemia, lymphoma and myeloma cell lines IC50s of 6.9 - 305 nM. APTO-253 produces significant tumor growth inhibition in the KG-1, THP-1 and Kasumi-1 xenograft models of human acute myeloid leukemia (AML).
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