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Details

Stereochemistry ACHIRAL
Molecular Formula C24H18ClFN4O2
Molecular Weight 448.877
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ALLITINIB

SMILES

FC1=CC(COC2=CC=C(NC3=C4C=C(NC(=O)C=C)C=CC4=NC=N3)C=C2Cl)=CC=C1

InChI

InChIKey=MVZGYPSXNDCANY-UHFFFAOYSA-N
InChI=1S/C24H18ClFN4O2/c1-2-23(31)29-17-6-8-21-19(11-17)24(28-14-27-21)30-18-7-9-22(20(25)12-18)32-13-15-4-3-5-16(26)10-15/h2-12,14H,1,13H2,(H,29,31)(H,27,28,30)

HIDE SMILES / InChI
Molecular Formula C24H18ClFN4O2
Molecular Weight 448.877
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: description was created based on several sources, including: https://www.ncbi.nlm.nih.gov/pubmed/24612546 | http://adisinsight.springer.com/drugs/800032292

AST-1306, also known as Allitinib, is an orally active potent, selective, irreversible inhibitor of the HER family of receptor tyrosine kinases. AST-1306 inhibits the enzymatic activities of wild-type epidermal growth factor receptor (EGFR) and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu) transgenic breast cancer mouse models. Allitinib is in Phase I clinical trial for the treatment of advanced solid tumors. Serious adverse effects detected were: diarrhea, dehydration and hyperbilirubinemia.

Originator

Allist Pharmaceuticals
1
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/21789172

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 0.5 nM [IC50]
Inhibitor
8297
 3.0 nM [IC50]
Inhibitor
8297
 0.8 nM [IC50]
Substrate
661
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase I
428
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Repositioning of Tyrosine Kinase Inhibitors as Antagonists of ATP-Binding Cassette Transporters in Anticancer Drug Resistance.
2014 Sep 29
Patents

Patents

US20140121126 A1
1
US20160002600 A1
1
WO2016191471 A1
1

Sample Use Guides

In Vivo Use Guide
1000 mg three times daily
Route of Administration: Oral
In Vitro Use Guide
The Calu-3 lung adenocarcinoma and BT474 breast cancer cell line, containing high levels of ErbB2, were more sensitive to AST1306, with IC50 values of 0.23 and 0.97 uM/L, respectively.
Substance Class Chemical
Created
by admin
on Sat Dec 16 15:55:03 GMT 2023
Edited
by admin
on Sat Dec 16 15:55:03 GMT 2023
Record UNII
CX0M5RO7CY
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ALLITINIB
Common Name English
AST1306
Common Name English
N-(4-((3-CHLORO-4-((3-FLUOROBENZYL)OXY)PHENYL)AMINO)QUINAZOLIN-6-YL)ACRYLAMIDE
Systematic Name English
ALS 1306
Common Name English
AST 1306
Common Name English
2-PROPENAMIDE, N-(4-((3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)AMINO)-6-QUINAZOLINYL)-
Systematic Name English
N-(4-((3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)AMINO)-6-QUINAZOLINYL)-2-PROPENAMIDE
Systematic Name English
Code System Code Type Description
FDA UNII
CX0M5RO7CY
Created by admin on Sat Dec 16 15:55:04 GMT 2023 , Edited by admin on Sat Dec 16 15:55:04 GMT 2023
PRIMARY
PUBCHEM
24739943
Created by admin on Sat Dec 16 15:55:04 GMT 2023 , Edited by admin on Sat Dec 16 15:55:04 GMT 2023
PRIMARY
EPA CompTox
DTXSID30647124
Created by admin on Sat Dec 16 15:55:04 GMT 2023 , Edited by admin on Sat Dec 16 15:55:04 GMT 2023
PRIMARY
NCI_THESAURUS
C179280
Created by admin on Sat Dec 16 15:55:04 GMT 2023 , Edited by admin on Sat Dec 16 15:55:04 GMT 2023
PRIMARY
CAS
897383-62-9
Created by admin on Sat Dec 16 15:55:04 GMT 2023 , Edited by admin on Sat Dec 16 15:55:04 GMT 2023
PRIMARY
Related Record Type Details
EPIDERMAL GROWTH FACTOR RECEPTOR
TARGET -> INHIBITOR
irreversible selective inhibitor
IRREVERSIBLE INHIBITOR
IC50
CYTOCHROME P450 3A5
METABOLIC ENZYME -> SUBSTRATE
MAJOR
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
MAJOR
RECEPTOR TYROSINE-PROTEIN KINASE ERBB-2
TARGET -> INHIBITOR
irreversible selective inhibitor
IRREVERSIBLE INHIBITOR
IC50
Structure of ALLITINIB
EXCRETED UNCHANGED
FECAL
CYTOCHROME P450 1A2
METABOLIC ENZYME -> SUBSTRATE
MAJOR
Related Record Type Details
Structure of N-(4-((3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)AMINO)-6-QUINAZOLINYL)-2,3-DIHYDROXYPROPANAMIDE
METABOLITE -> PARENT
FECAL; PLASMA; URINE
Structure of N-(4-(3-CHLORO-4-HYDROXY-ANILINO)QUINAZOLIN-6-YL)PROPANAMIDE
METABOLITE -> PARENT
FECAL; PLASMA
Structure of N-(4-((3-CHLORO-4-HYDROXYPHENYL)AMINO)-6-QUINAZOLINYL)-2,3-DIHYDROXYPROPANAMIDE
METABOLITE -> PARENT
FECAL; PLASMA; URINE
Structure of L-CYSTEINE, N-ACETYL-S-(3-((4-((3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)AMINO)-6-QUINAZOLINYL)AMINO)-3-OXOPROPYL)-
METABOLITE -> PARENT
URINE
Structure of (2S,3S,4S,5R,6S)-6-(6-AMINO-4-(3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)ANILINO)QUINAZOLIN-2-YL)OXY-3,4,5-TRIHYDROXY-TETRAHYDROPYRAN-2-CARBOXYLIC ACID
METABOLITE -> PARENT
PLASMA
Structure of (2R)-2-ACETAMIDO-3-(3-((4-(3-CHLORO-4-HYDROXY-ANILINO)QUINAZOLIN-6-YL)AMINO)-3-OXO-PROPYL)SULFANYL-PROPANOIC ACID
METABOLITE -> PARENT
FECAL
Structure of 6-AMINO-4-(3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)ANILINO)QUINAZOLIN-2-OL
METABOLITE -> PARENT
Structure of (2R)-2-AMINO-3-(3-((4-(3-CHLORO-4-HYDROXY-ANILINO)QUINAZOLIN-6-YL)AMINO)-3-OXO-PROPYL)SULFANYL-PROPANOIC ACID
METABOLITE -> PARENT
FECAL; URINE
Structure of N-(4-(3-CHLORO-4-HYDROXY-ANILINO)-2-HYDROXY-QUINAZOLIN-6-YL)PROP-2-ENAMIDE
METABOLITE -> PARENT
FECAL; URINE
Structure of 2-PROPENAMIDE, N-(4-((3-CHLORO-4-HYDROXYPHENYL)AMINO)-6-QUINAZOLINYL)-
METABOLITE -> PARENT
FECAL; PLASMA; URINE
Structure of (2-CHLORO-4-((2-HYDROXY-6-(PROP-2-ENOYLAMINO)QUINAZOLIN-4-YL)AMINO)PHENYL) HYDROGEN SULFATE
METABOLITE -> PARENT
URINE
Structure of N-(4-(3-CHLORO-4-HYDROXY-ANILINO)QUINAZOLIN-6-YL)-3-HYDROXY-PROPANAMIDE
METABOLITE -> PARENT
FECAL
Structure of 4,6-QUINAZOLINEDIAMINE, N4-(3-CHLORO-4-((3-FLUOROPHENYL)METHOXY)PHENYL)-
METABOLITE -> PARENT
FECAL; PLASMA; URINE
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC AT DAY 1

IN CANCER PATIENTS

THREE TIMES A DAY

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC IN CANCER PATIENTS

AT DAY 24

THREE TIMES A DAY FOR 21 DAYS

ORAL ADMINISTRATION

Biological Half-life PHARMACOKINETIC THREE TIMES A DAY

IN CANCER PATIENTS

AT DAY 1

ORAL ADMINISTRATION

Tmax PHARMACOKINETIC IN CANCER PATIENTS

AT DAY 24

THREE TIMES A DAY FOR 21 DAYS

ORAL ADMINISTRATION

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