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Tipifarnib

Tipifarnib structure

CAS No:
192185-72-1
Formula:
C27H22Cl2N4O
Chemical Name:
Tipifarnib
Synonyms:
2(1H)-Quinolinone,6-[(R)-amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-;6-[(R)-Amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone;Tipifarnib;(R)-(+)-R 115777;Zarnestra;2: PN: WO2019129231 SEQID: 3 claimed sequence
Categories:
Biochemical Engineering > Inhibitors

Description

Off-White to Pale Beige Solid

Tipifarnib is a quinolone that is 1-methylquinolin-2-one which carries a 3-chlorophenyl and an amino(4-chlorophenyl)(1-methyl-imidazol-5-yl)methyl groups at the 4 and 6 positions, respectively (the R-isomer). It has a role as an antineoplastic agent, an EC 2.5.1.58 (protein farnesyltransferase) inhibitor and an apoptosis inducer. It is a quinolone, a member of monochlorobenzenes, a member of imidazoles and a primary amino compound.|Tipifarnib (R-115777) is a substance that is being studied in the treatment of acute myeloid leukemia (AML) and other types of cancer. It belongs to the family of drugs called farnesyltransferase inhibitors. It is also called Zarnestra. In June 2005, the FDA issued a Not Approvable Letter for Zarnestra.|Tipifarnib is a nonpeptidomimetic quinolinone with potential antineoplastic activity. Tipifarnib binds to and inhibits the enzyme farnesyl protein transferase, an enzyme involved in protein processing (farnesylation) for signal transduction. By inhibiting the farnesylation of proteins, this agent prevents the activation of Ras oncogenes, inhibits cell growth, induces apoptosis, and inhibits angiogenesis. (NCI04)

Tipifarnib Basic Attributes

Molecular Weight：

489.4

Exact Mass：

489.40

UNII：

MAT637500A

DSSTox ID：

DTXSID5041140

NCI Thesaurus Code：

C1703

Characteristics

PSA：

64.2

XLogP3：

4.1

Appearance：

Off-white to pale beige solid

Density：

1.33±0.1 g/cm3(Predicted)

Melting Point：

234 °C

Boiling Point：

681.7±55.0 °C(Predicted)

Flash Point：

366.1±31.5 °C

Refractive Index：

1.672

Storage Conditions：

-20°C Freezer

Vapor Pressure：

1.94E-18mmHg at 25°C

Safety Information

GHS Classification：

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P340, P305+P351+P338, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, P405, and P501|The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.

Drug Information

Drug Indication：

Investigated for use/treatment in colorectal cancer, leukemia (myeloid), pancreatic cancer, and solid tumors.|Treatment of head and neck epithelial malignant neoplasms

Pharmacology：

R115777, a nonpeptidomimetic farnesyl transferase inhibitor, suppresses the growth of human pancreatic adenocarcinoma cell lines. This growth inhibition is associated with modulation in the phosphorylation levels of signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinases (ERK).

MeSH：

Substances that inhibit or prevent the proliferation of NEOPLASMS. (See all compounds classified as Antineoplastic Agents.)

Mechanism of Action：

The farnesyltransferase inhibitors (FTIs) are a class of experimental cancer drugs that target protein farnesyltransferase with the downstream effect of preventing the proper functioning of the Ras protein, which is commonly abnormally active in cancer. After translation, RAS goes through four steps of modification: isoprenylation, proteolysis, methylation and palmitoylation. Isoprenylation involves the enzyme farnesyltransferase (FTase) transferring a farnesyl group from farnesyl pyrophosphate (FPP) to the pre-RAS protein. Also, a related enzyme geranylgeranyltransferase I (GGTase I) has the ability to transfer a geranylgeranyl group to K and N-RAS. Farnesyl is necessary to attach RAS to the cell membrane. Without attachment to the cell membrane, RAS is not able to transfer signals from membrane receptors (Reuter et al., 2000).

MeSH Entry Terms：

(R)-6-(amino(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl)-4-(3-chlorophenyl)-1-methyl-2(1H)-quinolinone

Tipifarnib Use and Manufacturing

Uses

A farnesyltransferase inhibitor. Sensitizes human multiple myeloma cell to proteasome inhibition by blocking degradation of bortezomib(B675700)-induced aggresomes. Also shown toinhibit the growth of myeloid leukemia cell lines and primary leukemia cells by inducing apoptosis and cell-cycle blockage when combined with rapamycin(R124000).

Use Classification：

Human drugs -> Rare disease (orphan)|Human Drugs -> EU pediatric investigation plans

Computed Properties

Molecular Weight:489.4
XLogP3:4.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:4
Exact Mass:488.1170667
Monoisotopic Mass:488.1170667
Topological Polar Surface Area:64.2
Heavy Atom Count:34
Complexity:785
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

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