GUADECITABINE SODIUM

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C18H23N9O10P.Na
Molecular Weight	579.3931
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

[Na+].NC1=NC(=O)C2=C(N1)N(C=N2)[C@H]3C[C@H](O)[C@@H](COP([O-])(=O)O[C@H]4C[C@@H](O[C@@H]4CO)N5C=NC(N)=NC5=O)O3

InChI

InChIKey=XLHBNJPXFOZFNJ-BYKQGDNKSA-M

InChI=1S/C18H24N9O10P.Na/c19-16-22-6-27(18(31)25-16)12-2-8(9(3-28)35-12)37-38(32,33)34-4-10-7(29)1-11(36-10)26-5-21-13-14(26)23-17(20)24-15(13)30;/h5-12,28-29H,1-4H2,(H,32,33)(H2,19,25,31)(H3,20,23,24,30);/q;+1/p-1/t7-,8-,9+,10+,11+,12+;/m0./s1

HIDE SMILES / InChI

Molecular Formula	C18H23N9O10P
Molecular Weight	556.4033
Charge	-1
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	6 / 6
E/Z Centers	0
Optical Activity	UNSPECIFIED

Molecular Formula	Na
Molecular Weight	22.98976928
Charge	1
Count	MOL RATIO 1 MOL RATIO (average)

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description

Decitabine was first synthesized by Pliml and Sorm in the Institute of Organic Chemistry, Czechoslovak Academy of Sciences in 1964. Later, the drug was approved by FDA for the treatment of myelodysplastic syndromes in patients with cancer. Upon administration the decitabine is metabolized to the active phosphorylated metabolite which is incorporated into DNA and thus inhibits DNA methyltransferase (decitabine deplete DNMT1).

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 282	Binding Agent 1,076
DNA (cytosine-5)-methyltransferase 1 10	Inhibitor 8,504

Conditions

Condition	Modality	Targets	Highest Phase	Product
Myelodysplastic syndromes 61	Primary		Approved 8,583	DACOGEN

C_max

Value	Dose	Co-administered	Analyte	Population
77 ng/mL	15 mg/m² 3 times / day steady-state, intravenous		DECITABINE plasma	Homo sapiens
155 ng/mL	20 mg/m² 1 times / day multiple, intravenous		DECITABINE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
158 ng × h/mL	15 mg/m² 3 times / day steady-state, intravenous		DECITABINE plasma	Homo sapiens
802.81 ng × h/mL	20 mg/m² 1 times / day multiple, intravenous		DECITABINE plasma	Homo sapiens
750.82 ng × h/mL	35 mg 1 times / day multiple, oral	CEDAZURIDINE	DECITABINE plasma	Homo sapiens
150 ng × h/mL	20 mg/m² 1 times / day multiple, intravenous		DECITABINE plasma	Homo sapiens

T_1/2

Value	Dose	Co-administered	Analyte	Population
0.78 h	15 mg/m² 3 times / day steady-state, intravenous		DECITABINE plasma	Homo sapiens
0.2 h	20 mg/m² 1 times / day multiple, intravenous		DECITABINE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
99%			DECITABINE plasma	Homo sapiens

Doses

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Dose	Population	Adverse events
100 mg/m2 2 times / day steady, intravenous Highest studied dose	unhealthy, 52 years (range: 23 - 78 years)
20 mg/m2 1 times / day steady, intravenous Recommended\|MTD	unhealthy, 59 years (range: 42–79 years)	Other AEs: Anaemia, Lymphopenia...
15 mg/m2 1 times / day steady, intravenous	unhealthy, 61 years (range: 32–82 years)	DLT: Hyperbilirubinemia, Thrombocytopenia...
20 mg/m2 1 times / day multiple, subcutaneous	unhealthy, 65 years
15 mg/m2 3 times / day steady, intravenous Recommended	unhealthy, 70 years (range: 65-76 years)	Disc. AE: Anemia, Neutropenia... Other AEs: Neutropenia, Thrombocytopenia...

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AEs

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AE	Significance	Dose	Population
Anaemia	grade 1, 17%	20 mg/m2 1 times / day steady, intravenous Recommended\|MTD	unhealthy, 59 years (range: 42–79 years)
Leucopenia	grade 1, 17%	20 mg/m2 1 times / day steady, intravenous Recommended\|MTD	unhealthy, 59 years (range: 42–79 years)
Thrombocytopaenia	grade 1, 17%	20 mg/m2 1 times / day steady, intravenous Recommended\|MTD	unhealthy, 59 years (range: 42–79 years)
Lymphopenia	grade 2, 17%	20 mg/m2 1 times / day steady, intravenous Recommended\|MTD	unhealthy, 59 years (range: 42–79 years)
Neutropenia	grade 2, 17%	20 mg/m2 1 times / day steady, intravenous Recommended\|MTD	unhealthy, 59 years (range: 42–79 years)

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Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2,252	inhibitor 2,438 inducer 440	inhibitor 2,507	inhibitor 2,217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2,153 CYP2C19 2,057 P-gp 1,741	P-gp 2,052	CYP3A4/5 133 CYP2B6 669 CYP1A2 832 CYP2E1 131

Drug as perpetrator

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Target	Modality	Activity
CYP1A2 2,333	inducer 1,966	no
CYP1A2 2,333	inhibitor 4,027	no
CYP2B6 1,160	inducer 1,966	no
CYP2C19 2,141	inhibitor 4,027	no
CYP2C9 2,497	inducer 1,966	no

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Drug as victim

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Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 2,052	substrate 4,014	weak

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Tox targets

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Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2,263	inhibitor 2,237

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
3B Scientific (Wuhan) Corp	3B2-0249	http://www.3bsc.com/index/pro_info.php?id=19605
Aaron Chemicals	AR002OAT	http://www.aaronchem.com/2353-33-5
abcr GmbH	AB348661	http://www.abcr.com/shop/en/AB348661
AbMole Bioscience	M2052	http://www.abmole.com/products/decitabine.html
Achemtek	0102-022107	http://www.achemtek.com/2353-33-5

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PubMed

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Title	Date	PubMed
Autoreactive murine Th1 and Th2 cells kill syngeneic macrophages and induce autoantibodies.	2001	11530995
Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine.	2001 Apr	11259619
Biallelic inactivation of retinoic acid receptor beta2 gene by epigenetic change in breast cancer.	2001 Jan	11141504
Promoter hypermethylation: a common cause of reduced p16(INK4a) expression in uveal melanoma.	2001 Jul 1	11431374
Increased expression of unmethylated CDKN2D by 5-aza-2'-deoxycytidine in human lung cancer cells.	2001 Nov 22	11753657

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Sample Use Guides

In Vivo Use Guide

Guadecitabine 60 mg/m2 given subcutaneously daily on Days 1-5 in 28-day cycles. The total amount (in mg) of guadecitabine to be administered is determined by body surface area.

Route of Administration: Other

In Vitro Use Guide

AML cells were treated daily with serial dilutions (0.02–50 uM) of freshlyprepared decitabine and incubated at 37 degree Celsius, 5% CO2 for 72 hours.

Substance Class	Chemical
Record UNII	0RB89YH367
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

SGI-110 SODIUM SALT

Preferred Name

English

GUADECITABINE SODIUM

Official Name

English

GUANOSINE, 2'-DEOXY-5-AZACYTIDYLYL-(3'-5')-2'-DEOXY-, SODIUM SALT (1:1)

Common Name

English

GUADECITABINE SODIUM [JAN]

Common Name

English

GUADECITABINE SODIUM [USAN]

Common Name

English

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Classification Tree

Code System

Code

Positive

EU-Orphan Drug

EU/3/15/1597

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Code System

Code

Type

Description

DRUG BANK

DBSALT002105

PRIMARY

CAS

929904-85-8

PRIMARY

USAN

AB-43

PRIMARY

FDA UNII

0RB89YH367

PRIMARY

ChEMBL

CHEMBL3544916

PRIMARY

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Related Record

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Details


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GUADECITABINE

PARENT -> SALT/SOLVATE

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					2KT4YN1DP7

GUADECITABINE

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SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Overview

OverviewOther

Drug as perpetrator​

Drug as victim

Tox targets

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound

Drug as perpetrator