VTP-27999

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C26H41ClN4O5
Molecular Weight	525.081
Optical Activity	UNSPECIFIED
Defined Stereocenters	4 / 4
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@]1(CCCN(C1)C(=O)NC[C@H](C[C@H]2CCCOC2)NC)[C@@H](OCCNC(=O)OC)C3=CC=CC(Cl)=C3

InChI

InChIKey=NXWASIVXQMMPLM-ZXMXYHOLSA-N

InChI=1S/C26H41ClN4O5/c1-28-23(14-19-6-5-12-35-18-19)16-30-25(32)31-11-4-8-21(17-31)24(20-7-3-9-22(27)15-20)36-13-10-29-26(33)34-2/h3,7,9,15,19,21,23-24,28H,4-6,8,10-14,16-18H2,1-2H3,(H,29,33)(H,30,32)/t19-,21-,23+,24+/m1/s1

HIDE SMILES / InChI

Molecular Formula	C26H41ClN4O5
Molecular Weight	525.081
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	4 / 4
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://adisinsight.springer.com/drugs/800022684
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/24900262

VTP-27999 is an alkyl amine renin inhibitor. This compound demonstrated excellent selectivity over related and unrelated off-targets, >15% oral bioavailability in three species, oral efficacy in a double transgenic rat model of hypertension, and good exposure in humans. Vitae Pharmaceuticals was developing VTP 27999 for the treatment of chronic kidney disease. VTP 27999 was in phase I clinical development in the US. However, the product is no more on the company pipeline and it appears that the development has been discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Renin 7 Target ID: CHEMBL286 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24900262	Inhibitor 8297		0.47 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Chronic kidney disease 56 Sources: http://adisinsight.springer.com/drugs/800022684	Primary		Phase I 428	Unknown Approved Use Unknown
Hypertension 567 Sources: http://adisinsight.springer.com/drugs/800022684	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1736 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470465	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VTP-27999 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
1207 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470465	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		VTP-27999 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
13663 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470465	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VTP-27999 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
8466 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470465	600 mg single, oral dose: 600 mg route of administration: Oral experiment type: SINGLE co-administered:		VTP-27999 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
23.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/24470465	600 mg 1 times / day multiple, oral dose: 600 mg route of administration: Oral experiment type: MULTIPLE co-administered:		VTP-27999 plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	P-gp 1537

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/24900262/	no [IC50 >30 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363678228	no
CYP2D6 1891	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678228	yes [IC50 18.9991 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1537	substrate 3367 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678228	no

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY100632	https://www.001chemical.com/chem/search?q=DY100632
1PlusChem LLC	1P009CW9	https://www.1pchem.com/search?query=1P009CW9
AK Scientific	4154AH	https://aksci.com/item_detail.php?cat=4154AH
AK Scientific	6076AC	https://aksci.com/item_detail.php?cat=6076AC
AbovChem LLC	HY-50768	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-50768
Angene	AGN-PC-0ONTWP	http://www.angenechemical.com/productshow/AGN-PC-0ONTWP.html
AstaTech	A11418	http://astatechinc.com/CPSResult.php?CRNO=A11418
BLD Pharm	BD234851	http://www.bldpharm.com/search/Search.html?keyword=BD234851
BLD Pharm	BD629826	http://www.bldpharm.com/search/Search.html?keyword=BD629826
BLD Pharm	BD630075	http://www.bldpharm.com/search/Search.html?keyword=BD630075
BOC Sciences	1013937-63-7	http://www.bocsci.com/description.asp?cas=1013937-63-7
BOC Sciences	942142-51-0	http://www.bocsci.com/description.asp?cas=942142-51-0
ChemShuttle	178219	https://www.chemshuttle.com/catalogsearch/result/?q=178219
Matrix Scientific	96076	http://www.matrixscientific.com/096076.html
MedChem Express	HY-50769	https://www.medchemexpress.com/search.html?q=HY-50769&ft=&fa=&fp=
MedChem Express	HY-76652	https://www.medchemexpress.com/search.html?q=HY-76652&ft=&fa=&fp=
MolPort	MolPort-023-332-844	https://www.molport.com/shop/molecule-link/MolPort-023-332-844
MolPort	MolPort-039-338-063	https://www.molport.com/shop/molecule-link/MolPort-039-338-063
MolPort	MolPort-046-417-307	https://www.molport.com/shop/molecule-link/MolPort-046-417-307
Molcore	MC100632	http://www.molcore.com/CatMC100632.html
Molnova	M10079	https://www.molnova.com/en/serch-list.html?keywords=M10079
MuseChem	I010052	https://www.musechem.com/product/I010052.html
ShangHai Biochempartner	BCP10700	http://www.biochempartner.com/search_BCP10700
ShangHai Biochempartner	BCP27647	http://www.biochempartner.com/search_BCP27647
TargetMol	T3064	https://www.targetmol.com/search?keyword=T3064
Tocris	5563	https://www.tocris.com/search.php?Type=QuickSearch&Value=5563
Toronto Research Chemicals	P991798	https://www.trc-canada.com/product-detail/?CatNum=P991798
Toronto Research Chemicals	V785050	https://www.trc-canada.com/product-detail/?CatNum=V785050
Toronto Research Chemicals	V785055	https://www.trc-canada.com/product-detail/?CatNum=V785055
Wonderchem	WD0726P	http://www.wonder-chem.com/search.html?text=WD0726P
eMolecules	106929072	https://orderbb.emolecules.com/search/#?query=106929072
eMolecules	206919430	https://orderbb.emolecules.com/search/#?query=206919430
eMolecules	44467942	https://orderbb.emolecules.com/search/#?query=44467942
eMolecules	44811602	https://orderbb.emolecules.com/search/#?query=44811602
eMolecules	44811781	https://orderbb.emolecules.com/search/#?query=44811781
eNovation Chemicals	D388293	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D388293&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-3347382408	https://mcule.com/MCULE-3347382408/
mcule	MCULE-3742511536	https://mcule.com/MCULE-3742511536/
mcule	MCULE-8726731283	https://mcule.com/MCULE-8726731283/

PubMed

Title	Date	PubMed
Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for Clinical Utility.	2011 Oct 13	24900262
New renin inhibitor VTP-27999 alters renin immunoreactivity and does not unfold prorenin.	2013 May	23460288
Renin inhibitor VTP-27999 differs from aliskiren: focus on their intracellular accumulation and the (pro)renin receptor.	2014 Jun	24637873
Multiple ascending dose study with the new renin inhibitor VTP-27999: nephrocentric consequences of too much renin inhibition.	2014 May	24470465
Maximum renal responses to renin inhibition in healthy study participants: VTP-27999 versus aliskiren.	2016 May	26882043
Do prorenin-synthesizing cells release active, 'open' prorenin?	2017 Feb	28005703

Sample Use Guides

In Vivo Use Guide

The effects of escalating VTP-27999 doses (75-600 mg) on renal plasma flow, glomerular filtration rate (GFR), and plasma renin-angiotensin system components were compared with those of 300 mg aliskiren in 22 normal volunteers on a low-sodium diet. Maximum renal renin blockade in healthy, salt-depleted volunteers, requires aliskiren doses higher than 300 mg, but can be established with 300 mg VTP-27999. Excessive intrarenal renin inhibition, obtained at VTP-27999 doses of 300 mg and higher, is accompanied by plasma renin rises, that after stopping drug intake, exceed the capacity of extrarenal VTP-27999 to block fully the enzymatic reaction.

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Sat Dec 16 11:18:19 GMT 2023` Edited by `admin` on `Sat Dec 16 11:18:19 GMT 2023`
Record UNII	254XY8NV84
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

VTP-27999

Common Name

English

CARBAMIC ACID, N-(2-((R)-(3-CHLOROPHENYL)((3R)-1-((((2S)-2-(METHYLAMINO)-3-((3R)-TETRAHYDRO-2H-PYRAN-3-YL)PROPYL)AMINO)CARBONYL)-3-PIPERIDINYL)METHOXY)ETHYL)-, METHYL ESTER

Systematic Name

English

Code System Code Type Description

CAS

942142-51-0