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
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
DescriptionCurator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/24900262
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
Cmax
| 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 |
T1/2
| 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 |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no [IC50 >30 uM] | ||||
| no | ||||
| yes [IC50 18.9991 uM] |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| no |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Discovery of VTP-27999, an Alkyl Amine Renin Inhibitor with Potential for Clinical Utility. | 2011 Oct 13 |
|
| New renin inhibitor VTP-27999 alters renin immunoreactivity and does not unfold prorenin. | 2013 May |
|
| Renin inhibitor VTP-27999 differs from aliskiren: focus on their intracellular accumulation and the (pro)renin receptor. | 2014 Jun |
|
| Maximum renal responses to renin inhibition in healthy study participants: VTP-27999 versus aliskiren. | 2016 May |
|
| Do prorenin-synthesizing cells release active, 'open' prorenin? | 2017 Feb |
Sample Use Guides
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
| Name | Type | Language | ||
|---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English |
| Code System | Code | Type | Description | ||
|---|---|---|---|---|---|
|
942142-51-0
Created by
admin on Sat Dec 16 11:18:19 GMT 2023 , Edited by admin on Sat Dec 16 11:18:19 GMT 2023
|
PRIMARY | |||
|
16126898
Created by
admin on Sat Dec 16 11:18:19 GMT 2023 , Edited by admin on Sat Dec 16 11:18:19 GMT 2023
|
PRIMARY | |||
|
254XY8NV84
Created by
admin on Sat Dec 16 11:18:19 GMT 2023 , Edited by admin on Sat Dec 16 11:18:19 GMT 2023
|
PRIMARY | |||
|
DTXSID70583133
Created by
admin on Sat Dec 16 11:18:19 GMT 2023 , Edited by admin on Sat Dec 16 11:18:19 GMT 2023
|
PRIMARY | |||
|
DB12416
Created by
admin on Sat Dec 16 11:18:19 GMT 2023 , Edited by admin on Sat Dec 16 11:18:19 GMT 2023
|
PRIMARY |
ACTIVE MOIETY
