GGTI-2418

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C23H31N5O4
Molecular Weight	441.5233
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)C[C@H](NC(=O)N1CCN(CC2=C(C)N=CN2)C(=O)[C@@H]1CC3=CC=CC=C3)C(O)=O

InChI

InChIKey=COLCNDRDBCLVOC-ICSRJNTNSA-N

InChI=1S/C23H31N5O4/c1-15(2)11-18(22(30)31)26-23(32)28-10-9-27(13-19-16(3)24-14-25-19)21(29)20(28)12-17-7-5-4-6-8-17/h4-8,14-15,18,20H,9-13H2,1-3H3,(H,24,25)(H,26,32)(H,30,31)/t18-,20-/m0/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25530833

GGTI-2418, also known as PTX100, is a synthetic peptidomimetic inhibitor of geranylgeranyltransferase I (GGTase I) that appears to induce apoptosis by downregulating several pivotal oncogenic and tumor survival pathways. In preclinical studies, GGTI-2418 has been shown to cause significant breast tumor regression in ErbB2 transgenic mice model. GGTI-2418 was the first GGTase I inhibitor to enter clinical development in early 2009. Phase I clinical trials early results demonstrated that ~30% of patients with advanced solid tumors had stable disease following GGTI-2418 therapy, the compound was well-tolerated and had minimal toxicity. However, the Phase I trial of GGTI-2418 has been stopped due to its lack of efficacy in patients. In February 2015 Prescient Therapeutics in-licensed the p27 biomarker for use as a companion diagnostic. Patients with low levels of p27 are more likely to respond to GGTI-2418 therapy.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Geranylgeranyl transferase type I 7 Target ID: CHEMBL2095164 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25530833	Inhibitor 8297		9.5 nM [IC50]
Protein farnesyltransferase 13 Target ID: CHEMBL2094108 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25530833	Inhibitor 8297		53000.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Breast cancer 434 Sources: http://www.asx.com.au/asxpdf/20150610/pdf/42z391p5pfyh79.pdf	Primary		Phase II 1132	Unknown Approved Use Unknown
Solid tumors 145 Sources: http://adisinsight.springer.com/drugs/800030147	Primary		Phase I 428	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
93.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	750 mg/m² single, intravenous dose: 750 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
18.5 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
19 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	330 mg/m² 1 times / day multiple, intravenous dose: 330 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
160 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	1050 mg/m² single, intravenous dose: 1050 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
117 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	750 mg/m² 1 times / day multiple, intravenous dose: 750 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
226 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	1470 mg/m² 1 times / day multiple, intravenous dose: 1470 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
56.1 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	500 mg/m² single, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
209 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	2060 mg/m² single, intravenous dose: 2060 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
26.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
126 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	750 mg/m² single, intravenous dose: 750 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
15.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
16.2 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	330 mg/m² 1 times / day multiple, intravenous dose: 330 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
180 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	1050 mg/m² single, intravenous dose: 1050 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
186 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	750 mg/m² 1 times / day multiple, intravenous dose: 750 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
320 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	1470 mg/m² 1 times / day multiple, intravenous dose: 1470 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
36.3 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	500 mg/m² single, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
462 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	2060 mg/m² single, intravenous dose: 2060 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
21.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	750 mg/m² single, intravenous dose: 750 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	200 mg/m² single, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	330 mg/m² 1 times / day multiple, intravenous dose: 330 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	1050 mg/m² single, intravenous dose: 1050 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	750 mg/m² 1 times / day multiple, intravenous dose: 750 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	1470 mg/m² 1 times / day multiple, intravenous dose: 1470 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	500 mg/m² single, intravenous dose: 500 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
0.99 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	2060 mg/m² single, intravenous dose: 2060 mg/m² route of administration: Intravenous experiment type: SINGLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/31372813/	200 mg/m² 1 times / day multiple, intravenous dose: 200 mg/m² route of administration: Intravenous experiment type: MULTIPLE co-administered:	GGTI-2418 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
2060 mg/m2 1 times / day multiple, intravenous (unknown) MTD Dose: 2060 mg/m2, 1 times / day Route: intravenous Route: multiple Dose: 2060 mg/m2, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/31372813/	unhealthy n = 6 Health Status: unhealthy Condition: cancer Sex: M+F Food Status: UNKNOWN Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/31372813/	Sources: https://pubmed.ncbi.nlm.nih.gov/31372813/

Sourcing

Vendor/Aggregator	ID	URL
Chem Scene	CS-0006195	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0006195
Excenen	EX-A3132	http://www.excenen.com/searchresultlist.php?id=EX-A3132
Hairui	HR142132	http://www.hairuichem.com/en/product/search.do?q=HR142132
MedChem Express	HY-16231	https://www.medchemexpress.com/search.html?q=HY-16231&ft=&fa=&fp=
MolPort	MolPort-046-761-290	https://www.molport.com/shop/molecule-link/MolPort-046-761-290
MolPort	MolPort-046-788-442	https://www.molport.com/shop/molecule-link/MolPort-046-788-442
MuseChem	I008908	https://www.musechem.com/product/I008908.html
eMolecules	252373507	https://orderbb.emolecules.com/search/#?query=252373507
eMolecules	271383537	https://orderbb.emolecules.com/search/#?query=271383537
eMolecules	95699417	https://orderbb.emolecules.com/search/#?query=95699417

PubMed

Title	Date	PubMed

Patents

Sample Use Guides

In Vivo Use Guide

120 to 2060 mg/m2/day as a 30-min IV infusion on Days 1-5 every 21 days.

Route of Administration: Intravenous

In Vitro Use Guide

H-Ras-transformed NIH 3T3 cells were treated with various concentrations of GGTI-2418, and the cell lysates were separated on 12.5% SDS-PAGE. The separated proteins were transferred to nitrocellulose and immunoblotted using an anti-Ras antibody (Y13-258) or an anti-Rap1A antibody (SC-65, Santa Cruz Biotechnology, Santa Cruz, CA). Antibody reactions were visualized using either peroxidase-conjugated goat anti-rat IgG or goat anti-rabbit IgG and an enhanced chemiluminescence detection system.

Name

Type

Language

GGTI-2418

Common Name

English

PTX-100

Common Name

English

Classification Tree Code System Code

FDA ORPHAN DRUG

890422