TRIMETHYLCOLCHICINIC ACID

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H21NO5
Molecular Weight	343.3737
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=C(OC)C(OC)=C2C(CC[C@H](N)C3=CC(=O)C(O)=CC=C23)=C1

InChI

InChIKey=IRVWPZRYDQROLU-ZDUSSCGKSA-N

InChI=1S/C19H21NO5/c1-23-16-8-10-4-6-13(20)12-9-15(22)14(21)7-5-11(12)17(10)19(25-3)18(16)24-2/h5,7-9,13H,4,6,20H2,1-3H3,(H,21,22)/t13-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2208579 | https://www.ncbi.nlm.nih.gov/pubmed/9250535

Trimethylcolchicinic acid (also known as deacetyl colchicine) was used for patients with advanced malignancies. However, these studies were discontinued. Expeiments on rat were shown, that trimethylcolchicinic acid was able to improve normal liver histology, ultrastructure, collagen content and biochemical markers of liver damage in spite of that trimethylcolchicinic acid, didn't bind tubulin.

Approval Year

Conditions

Condition	Modality	Targets	Highest Phase	Product
Prostate cancer 178 Sources: https://www.ncbi.nlm.nih.gov/pubmed/2208579	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
30 μg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2208579	7 mg/m² 1 times / day multiple, oral dose: 7 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		TRIMETHYLCOLCHICINIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
41 μg/L EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x	5 mg/m² 1 times / day multiple, oral dose: 5 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		TRIMETHYLCOLCHICINIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
490 μg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2208579	7 mg/m² 1 times / day multiple, oral dose: 7 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		TRIMETHYLCOLCHICINIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
737 μg × h/L EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x	5 mg/m² 1 times / day multiple, oral dose: 5 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		TRIMETHYLCOLCHICINIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
9.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/2208579	7 mg/m² 1 times / day multiple, oral dose: 7 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		TRIMETHYLCOLCHICINIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED
10.7 h EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x	5 mg/m² 1 times / day multiple, oral dose: 5 mg/m² route of administration: Oral experiment type: MULTIPLE co-administered:		TRIMETHYLCOLCHICINIC ACID plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
7 mg/m2 1 times / day multiple, oral Highest studied dose Dose: 7 mg/m2, 1 times / day Route: oral Route: multiple Dose: 7 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2208579 Page: p.360, 361	unhealthy, ADULT n = 2 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M Food Status: FASTED Population Size: 2 Sources: https://pubmed.ncbi.nlm.nih.gov/2208579 Page: p.360, 361	Disc. AE: Skin erythema, Fever... Other AEs: Neutropenia... AEs leading to discontinuation/dose reduction: Skin erythema (grade 3, 50%) Fever (grade 3, 50%) Hypotension (grade 3, 50%) Multiple organ failure (grade 5, 50%) Mucositis (50%) Hepatic insufficiency (50%) Renal insufficiency (50%) Disseminated intravascular coagulation (grade 3, 50%) Neutropenia (50%) Other AEs: Neutropenia (grade 4, 50%) Sources: https://pubmed.ncbi.nlm.nih.gov/2208579 Page: p.360, 361
5 mg/m2 1 times / day multiple, oral RP2D Dose: 5 mg/m2, 1 times / day Route: oral Route: multiple Dose: 5 mg/m2, 1 times / day Sources: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x Page: p.198,199	unhealthy, ADULT n = 12 Health Status: unhealthy Condition: prostate cancer Age Group: ADULT Sex: M Food Status: FASTED Population Size: 12 Sources: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x Page: p.198,199	Disc. AE: Neutropenia, Neutropenic fever... Other AEs: Stomatitis, Neutropenic fever... AEs leading to discontinuation/dose reduction: Neutropenia (grade 4, 25%) Neutropenic fever (grade 5, 8.3%) Other AEs: Stomatitis (grade 3-4, 8.3%) Neutropenic fever (25%) Sources: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x Page: p.198,199
5 mg/m2 1 times / day multiple, oral RP2D Dose: 5 mg/m2, 1 times / day Route: oral Route: multiple Dose: 5 mg/m2, 1 times / day Sources: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x Page: p.198,199	unhealthy, ADULT n = 6 Health Status: unhealthy Condition: prostate cancer Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x Page: p.198,199	Disc. AE: Neutropenia... Other AEs: Stomatitis, Neutropenic fever... AEs leading to discontinuation/dose reduction: Neutropenia (grade 3-4, 100%) Other AEs: Stomatitis (grade 3-4, 50%) Neutropenic fever (50%) Sources: https://onlinelibrary.wiley.com/doi/abs/10.1046/j.1525-1411.1999.14010.x Page: p.198,199
5 mg/m2 1 times / day multiple, oral RP2D Dose: 5 mg/m2, 1 times / day Route: oral Route: multiple Dose: 5 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2208579 Page: p.360, 361	unhealthy, ADULT n = 11 Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: FASTED Population Size: 11 Sources: https://pubmed.ncbi.nlm.nih.gov/2208579 Page: p.360, 361	Disc. AE: Elevated liver enzymes... AEs leading to discontinuation/dose reduction: Elevated liver enzymes (9%) Sources: https://pubmed.ncbi.nlm.nih.gov/2208579 Page: p.360, 361

AEs

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inducer 781	inducer 389		inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461		CYP2E1 128 CYP1A2 701

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/11144118/	no
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1347076#sid=56463112	no
CYP2C9 1819	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/11144118/	weak
CYP2E1 970	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/11144118/	yes
CYP3A4 1925	inducer 1573 Sources: https://pubmed.ncbi.nlm.nih.gov/11144118/	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/720551#sid=56463112

Sourcing

Vendor/Aggregator	ID	URL
Alfa Chemistry	211409	http://www.alfa-chemistry.com/search.aspx?q=211409
Alfa Chemistry	ACM3482379	http://www.alfa-chemistry.com/search.aspx?q=ACM3482379
Alfa Chemistry	ACM68296640	http://www.alfa-chemistry.com/search.aspx?q=ACM68296640
Hairui	HR142468	http://www.hairuichem.com/en/product/search.do?q=HR142468
MolPort	MolPort-006-115-382	https://www.molport.com/shop/molecule-link/MolPort-006-115-382
MuseChem	R002399	https://www.musechem.com/product/R002399.html
Tetrahedron	TS78648	http://www.thsci.com/search.do?q=TS78648
Toronto Research Chemicals	B327027	https://www.trc-canada.com/product-detail/?CatNum=B327027
Toronto Research Chemicals	D198895	https://www.trc-canada.com/product-detail/?CatNum=D198895
Toronto Research Chemicals	D198900	https://www.trc-canada.com/product-detail/?CatNum=D198900
Toronto Research Chemicals	P705110	https://www.trc-canada.com/product-detail/?CatNum=P705110
Vitas-M Laboratory	STL564563	http://www.vitasmlab.biz/search/STL564563
eMolecules	42677778	https://orderbb.emolecules.com/search/#?query=42677778
eMolecules	42851761	https://orderbb.emolecules.com/search/#?query=42851761
eMolecules	72975826	https://orderbb.emolecules.com/search/#?query=72975826
mcule	MCULE-5880669800	https://mcule.com/MCULE-5880669800/

PubMed

Title	Date	PubMed
Phase I toxicity and pharmacology study of trimethylcolchicinic acid in patients with advanced malignancies.	1990	2208579
Anti-AIDS agents, 3. Inhibitory effects of colchicine derivatives on HIV replication in H9 lymphocyte cells.	1991 Mar-Apr	1919593
Comparative study of colchicine and trimethylcolchicinic acid on prolonged bile duct obstruction in the rat.	1996 May-Jun	8818870

Patents

Sample Use Guides

In Vivo Use Guide

once daily for 5 days every 3rd week

Route of Administration: Oral

In Vitro Use Guide

Unknown

Name

Type

Language

TRIMETHYLCOLCHICINIC ACID

Common Name

English

N-DEACETYLCOLCHICEINE

Common Name

English

NSC-36796

Code

English

COLCHICEINE, N-DEACETYL-

Common Name

English

DESACETYLCOLCHICEINE

Common Name

English

COLCHICINIC ACID, O,O',O''-TRIMETHYL-

Common Name

English

BENZO(A)HEPTALEN-9(5H)-ONE, 7-AMINO-6,7-DIHYDRO-10-HYDROXY-1,2,3-TRIMETHOXY-, (7S)-

Systematic Name

English

DEACETYLCOLCHICEINE

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C67421