9-AMINOCAMPTOTHECIN

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H17N3O4
Molecular Weight	363.3667
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CC[C@@]1(O)C(=O)OCC2=C1C=C3N(CC4=C3N=C5C=CC=C(N)C5=C4)C2=O

InChI

InChIKey=FUXVKZWTXQUGMW-FQEVSTJZSA-N

InChI=1S/C20H17N3O4/c1-2-20(26)13-7-16-17-10(6-11-14(21)4-3-5-15(11)22-17)8-23(16)18(24)12(13)9-27-19(20)25/h3-7,26H,2,8-9,21H2,1H3/t20-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C20H17N3O4
Molecular Weight	363.3667
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

Rubitecan [Orathecin™] is a topoisomerase I inhibitor extracted from the bark and leaves of the Camptotheca acuminata tree, which is native to China. Rubitecan is an oral compound being developed for the treatment of pancreatic cancer and other solid tumours by SuperGen. Rubitecan binds to and inhibits the enzyme topoisomerase I and induces protein-linked DNA single-strand breaks, thereby blocking DNA and RNA synthesis in dividing cells; this agent also prevents repair of reversible single-strand DNA breaks.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
cell proliferation 28	Inhibitor 8,297	0.17 µM [IC50]
Topoisomerase I 4	Inhibitor 8,297	12.0 nM [IC50]
DNA topoisomerase I 59	Inhibitor 8,297

Conditions

Condition	Modality	Highest Phase	Product
Colorectal cancer 101	Primary	Phase II 1,132	Unknown
Non-small cell lung cancer 206	Primary	Phase II 1,132	Unknown
Ovarian cancer 157	Primary	Phase II 1,132	Unknown
Kidney cancer 10	Primary	Phase II 1,132	Unknown
Lymphoma 58	Primary	Phase II 1,132	Unknown
Pancreatic cancer 97	Primary	Withdrawn	Unknown
Hepatocellular carcinoma 83	Primary	Basic research	Unknown
Melanoma 88	Primary	Phase II 1,132	Unknown
Ovarian cancer 157	Primary	Phase II 1,132	Unknown
Peritoneal cancer 11	Primary	Phase II 1,132	Unknown
Chronic myelomonocytic leukemia 5	Primary	Preclinical	Unknown

C_max

Value	Dose	Analyte	Population
26.1 ng/mL	1.5 mg/m² single, oral	RUBITECAN plasma	Homo sapiens
52.9 ng/mL	1.5 mg/m² single, oral	RUBITECAN plasma	Homo sapiens
115.56 ng/mL	1.5 mg/m² single, oral	RUBITECAN plasma	Homo sapiens
85.98 ng/mL	1.5 mg 1 times / day steady-state, oral	RUBITECAN plasma	Homo sapiens
147.57 ng/mL	1.75 mg/m² single, oral	9-AMINOCAMPTOTHECIN plasma	Homo sapiens
85.98 ng/mL	1.5 mg/m² 1 times / day multiple, oral	9-AMINOCAMPTOTHECIN plasma	Homo sapiens

AUC

Value	Dose	Analyte	Population
330 ng × h/mL	1.5 mg/m² single, oral	RUBITECAN plasma	Homo sapiens
557 ng × h/mL	1.5 mg/m² single, oral	RUBITECAN plasma	Homo sapiens
1047.35 ng × h/mL	1.5 mg/m² single, oral	RUBITECAN plasma	Homo sapiens
2214.92 ng × h/mL	1.5 mg 1 times / day steady-state, oral	RUBITECAN plasma	Homo sapiens
1385.39 ng × h/mL	1.75 mg/m² single, oral	9-AMINOCAMPTOTHECIN plasma	Homo sapiens
2214.92 ng × h/mL	1.5 mg/m² 1 times / day multiple, oral	9-AMINOCAMPTOTHECIN plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
9.17 h	1.5 mg/m² single, oral	RUBITECAN plasma	Homo sapiens
21.25 h	1.5 mg 1 times / day steady-state, oral	RUBITECAN plasma	Homo sapiens
8.65 h	1.75 mg/m² single, oral	9-AMINOCAMPTOTHECIN plasma	Homo sapiens
21.25 h	1.5 mg/m² 1 times / day multiple, oral	9-AMINOCAMPTOTHECIN plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1.5 mg/m2 1 times / day multiple, oral MTD	unhealthy, ADULT n = 10	DLT: Neutropenia, Anemia...
2 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, ADULT n = 26	DLT: Thrombocytopenia, Anemia...
0.7 mg/m2 1 times / day multiple, oral Highest studied dose	unhealthy, ADULT n = 3	DLT: anemia, neutropenia...
60 ug/m2 1 times / day multiple, intravenous Highest studied dose	unhealthy, ADULT n = 3	DLT: neutropenia...
0.63 mg/m2 1 times / day multiple, oral MTD	unhealthy, ADULT n = 5

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AEs

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AE	Significance	Dose	Population
Anemia	grade 4, 10% DLT	1.5 mg/m2 1 times / day multiple, oral MTD	unhealthy, ADULT n = 10
Neutropenia	grade 4, 10% DLT	1.5 mg/m2 1 times / day multiple, oral MTD	unhealthy, ADULT n = 10
Chemical cystitis	grade 3, 14% DLT	2 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, ADULT n = 26
Diarrhea	grade 3, 14% DLT	2 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, ADULT n = 26
Nausea	grade 3, 18% DLT	2 mg/m2 1 times / day multiple, oral Studied dose	unhealthy, ADULT n = 26

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
001 Chemical	DY113540	https://www.001chemical.com/chem/search?q=DY113540
001 Chemical	DY115137	https://www.001chemical.com/chem/search?q=DY115137
1PlusChem LLC	1P003O0O	https://www.1pchem.com/search?query=1P003O0O
1PlusChem LLC	1P003O27	https://www.1pchem.com/search?query=1P003O27
A2B Chem	AB70296	http://a2bchem.com/prod/AB70296

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PubMed

Show entries

Title	Date	PubMed
Inhibitors of human immunodeficiency virus integrase.	1993 Mar 15	8460151
Development of an optimal pharmacokinetic sampling schedule for rubitecan administered orally in a daily times five schedule.	2002 Dec	12451480
Enzyme-activated Prodrug Therapy Enhances Tumor-specific Replication of Adenovirus Vectors.	2002 Nov 1	12414633
Anisomycin activates JNK and sensitises DU 145 prostate carcinoma cells to Fas mediated apoptosis.	2002 Nov 4	12402161
Phase I and pharmacologic study of i.p. 9-aminocamptothecin given as six fractions over 14 days.	2002 Sep	12394266

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Patents

Sample Use Guides

In Vivo Use Guide

In phase I clinical trial 9-aminocamptothecin was administered intravenously as a 72-hour infusion. Different administration schedules were investigated in phase II trials.

Route of Administration: Intravenous

In Vitro Use Guide

In vitro anti-tumor efficacy of 9-aminocamptothecin (9-AC) was measured using growth inhibition assay in L1210 murine leukemia cells. 9-AC inhibited the proliferation of L1210 cells by 50% upon continues exposure at a concentration of 0.9 uM.

Substance Class	Chemical
Record UNII	5MB77ICE2Q
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

9-AMINOCAMPTOTHECIN

Common Name

English

1H-PYRANO(3',4':6,7)INDOLIZINO(1,2-B)QUINOLINE-3,14(4H,12H)-DIONE, 10-AMINO-4-ETHYL-4-HYDROXY-, (4S)-

Systematic Name

English

9-AMINO-20(S)-CAMPTOTHECIN

Common Name

English

9-AMINOCAMPTOTHECIN [MI]

Common Name

English

AMINOCAMPTOTHECIN

Common Name

English

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Classification Tree

Code System

Code

Topoisomerase-I Inhibitor

NCI_THESAURUS

C2843

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Code System

Code

Type

Description

DRUG BANK

DB12515

PRIMARY

FDA UNII

5MB77ICE2Q

PRIMARY

EPA CompTox

DTXSID10873202

PRIMARY

MESH

C080125

PRIMARY

NCI_THESAURUS

C1488

PRIMARY

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9-AMINOCAMPTOTHECIN

ACTIVE MOIETY

Amount:

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2