# US 10,946,012 B2 · Methods for inducing tumor regression, inhibiting tumor growth, and inducing apoptosis in breast tumors with geranylgeranyltransferase I inhibitors

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 10,946,012 B2
- Document ID: US10946012B2
- Status: Granted
- Kind: B2
- Application number: 13/194,022
- Filed: 2011-07-29
- Published: 2012-02-09
- Granted: 2021-03-16
- Earliest claimed: 2009-01-29
- Assignees: H. Lee Moffitt Cancer Center and Research Institute, Inc.; Yale University
- Applicants: Said M. Sebti; Andrew D. Hamilton
- Inventors: Said M. Sebti; Andrew D. Hamilton
- Web page: https://patentgrep.com/patent/US10946012B2

## CPC

- A61K 31/496: Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
- A61P 35/00: Antineoplastic agents
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Methods of inducing tumor regression, inhibiting tumor growth, and inducing apoptosis with selective peptidomimetic inhibitors of geranylgeranyltransferase I (GGTase I), are provided. In one aspect, GGTI-2418 and its methylester GGTI-2417, increase levels of the cyclin-dependent kinase (Cdk) inhibitor p27Kip1 and induce breast tumor regression in vivo. In another aspect, GGTI-2417 inhibits the Cdk2-mediated phosphorylation of p27Kip1 at Thr187 and accumulates p27Kip1 in the nucleus.

## Claims

### Claim 1

A method of treating breast cancer in a subject in need thereof, comprising:
assaying a breast cancer sample comprising breast cancer cells from the subject for nuclear p27 levels;
comparing the nuclear p27 levels to a control level of nuclear p27;
detecting breast cancer cells in the breast cancer sample having nuclear p27 levels that are below control levels of nuclear p27; and
administering a therapeutically effective amount of GGTI-2418 to the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein the effective amount is 100 mg/kg/day.

### Claim 3 (depends on 1)

The method of claim 1, wherein the effective amount is 200 mg/kg every third day.

### Claim 4 (depends on 1)

The method of claim 1, wherein the administration is performed by intraperitoneal injection.