NEO-212

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C17H20N6O4
Molecular Weight	372.3785
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

CN1N=NC2=C(N=CN2C1=O)C(=O)NC(=O)OCC3=CC[C@H](CC3)C(C)=C

InChI

InChIKey=MGTLGARADRIKNV-GFCCVEGCSA-N

InChI=1S/C17H20N6O4/c1-10(2)12-6-4-11(5-7-12)8-27-16(25)19-15(24)13-14-20-21-22(3)17(26)23(14)9-18-13/h4,9,12H,1,5-8H2,2-3H3,(H,19,24,25)/t12-/m1/s1

HIDE SMILES / InChI

Description

NEO 212 is novel DNA alkylating agent exhibiting superior activity against breast cancer cells in vitro and intracranial triple-negative tumor growth in vivo. NEO212 is a conjugate of temozolomide (TMZ,) with the natural product perillyl alcohol (POH). NEO 212 causes DNA damage and cell death much more efficiently than TMZ because linkage with POH increased it's biological half-life and thus provided greater opportunity for placement of cytotoxic DNA lesions.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
DNA 278	Crosslinking Agent 81
DNA 278	Blocker 537

Conditions

Condition	Modality	Highest Phase	Product
Glioblastoma multiforme 30	Primary	Approved 8,429	TEMODAR
Refractory anaplastic astrocytoma 2	Primary	Approved 8,429	TEMODAR
Cancer 592	Primary	Basic research	Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
7.5 μg/mL	150 mg/m² single, oral		TEMOZOLOMIDE plasma	Homo sapiens

AUC

Value	Dose	Co-administered	Analyte	Population
23.4 μg × h/mL	150 mg/m² single, oral		TEMOZOLOMIDE plasma	Homo sapiens

T_1/2

Value	Dose	Analyte	Population
1.89 h	200 mg/m^2 single, oral	TEMOZOLOMIDE plasma	Homo sapiens
1.87 h	200 mg/m^2 single, oral	TEMOZOLOMIDE plasma	Homo sapiens
1.8 h	150 mg/m² single, oral	TEMOZOLOMIDE plasma	Homo sapiens

F_unbound

Value	Dose	Co-administered	Analyte	Population
85%	150 mg/m² single, oral		TEMOZOLOMIDE plasma	Homo sapiens

Doses

Show entries

Dose	Population	Adverse events
1000 mg/m2 1 times / 4 weeks multiple, oral Highest studied dose	unhealthy, adult	Other AEs: Neutropenia, Thrombocytopenia...
250 mg/m2 1 times / day multiple, oral Highest studied dose	unhealthy, adult	DLT: Thrombocytopenia... Other AEs: Anaemia, Neutropenia...
200 mg/m2 1 times / day multiple, oral MTD	unhealthy, adult	Other AEs: Anaemia...
750 mg/m2 1 times / 4 weeks multiple, oral MTD	unhealthy, adult	Other AEs: Neutropenia, Thrombocytopenia...
150 mg/m2 1 times / day multiple, oral Recommended	unhealthy, adult	Other AEs: Anorexia, Dizziness...

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AEs

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AE	Significance	Dose	Population
Thrombocytopenia	grade 4, 1 patient	1000 mg/m2 1 times / 4 weeks multiple, oral Highest studied dose	unhealthy, adult
Neutropenia	grade 4, 2 patients	1000 mg/m2 1 times / 4 weeks multiple, oral Highest studied dose	unhealthy, adult
Anaemia	grade 3, 1 patient	250 mg/m2 1 times / day multiple, oral Highest studied dose	unhealthy, adult
Neutropenia	grade 3, 2 patients	250 mg/m2 1 times / day multiple, oral Highest studied dose	unhealthy, adult
Thrombocytopenia	grade 4, 2 patients DLT	250 mg/m2 1 times / day multiple, oral Highest studied dose	unhealthy, adult

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Sourcing

Sourcing

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Vendor/Aggregator	ID	URL
ChEBI	CHEBI:72564	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:72564
ChemicalBook	CB2708199	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB2708199
eMolecules	745657	https://www.emolecules.com/cgi-bin/more?vid=745657
MolPort	MolPort-003-850-406	https://www.molport.com/shop/molecule-link/MolPort-003-850-406
Selleck Chemicals	Methazolastone	http://www.selleckchem.com/products/Methazolastone.html

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PubMed

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Title	Date	PubMed
In vivo administration of O(6)-benzylguanine does not influence apoptosis or mutation frequency following DNA damage in the murine intestine, but does inhibit P450-dependent activation of dacarbazine.	2000 Apr	10753191
Temozolomide and treatment of malignant glioma.	2000 Jul	10914698
Temozolomide in malignant gliomas.	2000 Jun	10866347
Effect of O6-benzylguanine on alkylating agent-induced toxicity and mutagenicity. In Chinese hamster ovary cells expressing wild-type and mutant O6-alkylguanine-DNA alkyltransferases.	2000 Oct 1	11034089
Therapeutic management of refractory or relapsed primary central nervous system lymphomas.	2001	11757691

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Patents

Sample Use Guides

In Vivo Use Guide

intravenous infusion over 90 minutes is the same as the dose for the oral capsule formulation. Bioequivalence has been established only when TEMODAR for Injection was given over 90 minutes.

Route of Administration: Intravenous

In Vitro Use Guide

Grade IV glioma cell lines SHG44 and U251 cells were treated with 100 µmol/LT EMOZOLOMIDE (TMZ)

Show entries

Name

Type

Language

NEO-212

Common Name

English

CARBAMIC ACID, N-((3,4-DIHYDRO-3-METHYL-4-OXOIMIDAZO(5,1-D)-1,2,3,5-TETRAZIN-8-YL)CARBONYL)-, ((4S)-4-(1-METHYLETHENYL)-1-CYCLOHEXEN-1-YL)METHYL ESTER

Systematic Name

English

(S)-PERILLYL ALCOHOL TEMOZOLOMIDE CARBAMATE

Common Name

English

TMZ-POH CARBAMATE

Common Name

English

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Classification Tree

Code System

Code

Designated

FDA ORPHAN DRUG

557316

Designated

FDA ORPHAN DRUG

575117

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Code System

Code

Type

Description

PUBCHEM

56846912

PRIMARY

CAS

1361198-79-9

PRIMARY

FDA UNII

237TB781D9

PRIMARY

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ACTIVE MOIETY


					YF1K15M17Y

TEMOZOLOMIDE

SUBSTANCE RECORD


					237TB781D9

NEO-212

SMILES

InChI

CNS Activity

Originator

Approval Year

Targets

Conditions

Cmax

AUC

T1/2

Funbound

Doses

AEs

Sourcing

PubMed

Patents

Sample Use Guides

C_max

T_1/2

F_unbound