Pivaloyloxymethyl Butyrate(Pivaloyloxymethyl Butyrate) - 药物靶点：HDACs_专利_临床

概要

基本信息

药物类型

小分子化药

别名

Pivaloyloxymethylbutyrate、Pivanex

+ [1]

靶点

HDACs

作用机制

HDAC抑制剂(组蛋白去乙酰化酶家族抑制剂)

治疗领域

肿瘤免疫系统疾病消化系统疾病+ [3]

在研适应症-

非在研适应症

晚期非小细胞肺癌慢性淋巴细胞白血病肝癌+ [3]

原研机构

Bar-Ilan University

在研机构-

非在研机构

Bar-Ilan University

Titan Pharmaceuticals, Inc.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构

分子式C10H18O4

InChIKeyGYKLFBYWXZYSOW-UHFFFAOYSA-N

CAS号122110-53-6

关联

3

项与 Pivaloyloxymethyl Butyrate 相关的临床试验

NCT00083473 / Terminated临床2期

A Pilot Study of Pivanex, a Histone Deacetylase Inhibitor, in Patients With Chronic Lymphocytic Leukemia

This pilot study will assess the safety and efficacy of Pivanex alone in patients with chronic lymphocytic leukemia (CLL) who have relapsed or refractory disease after previous chemotherapy treatment. Pivanex is an investigational agent.

开始日期2004-05-01

申办/合作机构

Titan Pharmaceuticals, Inc.

NCT00087477 / Terminated临床1/2期

A Pilot Study of Pivanex, a Histone Deacetylase Inhibitor, in Patients With Malignant Melanoma

This pilot study will assess the safety and efficacy of Pivanex alone in patients with malignant melanoma who have relapsed after treatment with chemotherapy or Interleukin-2 (IL-2). Pivanex is an investigational agent.

开始日期2004-01-01

申办/合作机构

Titan Pharmaceuticals, Inc.

NCT00073385 / Completed临床2期

A Randomized Trial of Pivanex Plus Docetaxel or Docetaxel Monotherapy in Patients With Chemotherapy Resistant Advanced Non-Small Cell Carcinoma of the Lung (NSCLC)

This randomized study will assess the efficacy and safety of the combination of Pivanex and docetaxel compared to docetaxel alone in patients with a type of lung cancer called non-small cell lung cancer. Pivanex is an investigational agent, and docetaxel is an approved drug.

开始日期2003-09-01

申办/合作机构

Titan Pharmaceuticals, Inc.

100 项与 Pivaloyloxymethyl Butyrate 相关的临床结果

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100 项与 Pivaloyloxymethyl Butyrate 相关的转化医学

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100 项与 Pivaloyloxymethyl Butyrate 相关的专利（医药）

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35

项与 Pivaloyloxymethyl Butyrate 相关的文献（医药）

2022-06-01·Cancer Chemotherapy and Pharmacology4区 · 医学

An evaluation of the interaction of pixantrone with formaldehyde-releasing drugs in cancer cells

4区 · 医学

Article

作者: Phillips, Don R ; Evison, Benny J ; Mansour, Oula C ; Nudelman, Abraham ; Rephaeli, Ada ; Cutts, Suzanne M

PURPOSEPixantrone is a synthetic aza-anthracenedione currently used in the treatment of non-Hodgkin's lymphoma. The drug is firmly established as a poison of the nuclear enzyme topoisomerase II, however, pixantrone can also generate covalent drug-DNA adducts following activation by formaldehyde. While pixantrone-DNA adducts form proficiently in vitro, little evidence is presently at hand to indicate their existence within cells. The molecular nature of these lesions within cancer cells exposed to pixantrone and formaldehyde-releasing prodrugs was characterized along with the cellular responses to their formation.METHODSIn vitro crosslinking assays, [¹⁴C] scintillation counting analyses and alkaline comet assays were applied to characterize pixantrone-DNA adducts. Flow cytometry, cell growth inhibition and clonogenic assays were used to measure cancer cell kill and survival.RESULTSPixantrone-DNA adducts were not detectable in MCF-7 breast cancer cells exposed to [¹⁴C] pixantrone (10-40 µM) alone, however the addition of the formaldehyde-releasing prodrug AN9 yielded readily measurable levels of the lesion at ~ 1 adduct per 10 kb of genomic DNA. Co-administration with AN9 completely reversed topoisomerase II-associated DNA damage induction by pixantrone yet potentiated cell kill by the drug, suggesting that pixantrone-DNA adducts may promote a topoisomerase II-independent mechanism of cell death. Pixantrone-DNA adduct-forming treatments generally conferred mild synergism in multiple cell lines in various cell death and clonogenic assays, while pixantrone analogues either incapable or relatively defective in forming DNA adducts demonstrated antagonism when combined with AN9.CONCLUSIONSThe features unique to pixantrone-DNA adducts may be leveraged to enhance cancer cell kill and may be used to guide the design of pixantrone analogues that generate adducts with more favorable anticancer properties.

2021-03-01·Biochemical Pharmacology2区 · 医学

A switch in mechanism of action prevents doxorubicin-mediated cardiac damage

2区 · 医学

Article

作者: Lock, Peter ; Pepe, Salvatore ; Cheong, Alison ; Rephaeli, Ada ; Nudelman, Abraham ; Parker, Belinda S ; Maliki, Ruqaya ; Spurling, Alex ; McGrath, Sean ; Robinson, Tina ; Cutts, Suzanne M

Cancer patients treated with doxorubicin are at risk of congestive heart failure due to doxorubicin-mediated cardiotoxicity via topoisomerase IIβ poisoning. Acute cardiac muscle damage occurs in response to the very first dose of doxorubicin, however, cardioprotection has been reported after co-treatment of doxorubicin with acyloxyalkyl ester prodrugs. The aim of this study was to examine the role played by various forms of acute cardiac damage mediated by doxorubicin and determine a mechanism for the cardioprotective effect of formaldehyde-releasing prodrug AN-9 (pivaloyloxymethyl butyrate). Doxorubicin-induced cardiac damage in BALB/c mice bearing mammary tumours was established with a single dose of doxorubicin (4 or 16 mg/kg) administered alone or in combination with AN-9 (100 mg/kg). AN-9 protected the heart from doxorubicin-induced myocardial apoptosis and also significantly reduced dsDNA breaks, independent from the level of doxorubicin biodistribution to the heart. Covalent incorporation of [¹⁴C]doxorubicin into DNA showed that the combination treatment yielded significantly higher levels of formaldehyde-mediated doxorubicin-DNA adducts compared to doxorubicin alone, yet this form of damage was associated with cardioprotection from apoptosis. The cardiac transcriptomic analysis indicates that the combination treatment initiates inflammatory response signalling pathways. Doxorubicin and AN-9 combination treatments were cardioprotective, yet preserved doxorubicin-mediated anti-tumour proliferation and apoptosis in mammary tumours. This was associated with a switch in doxorubicin action from cardiac topoisomerase IIβ poisoning to covalent-DNA adduct formation. Co-administration of doxorubicin and formaldehyde-releasing prodrugs, such as AN-9, may be a promising cardioprotective therapy while maintaining doxorubicin activity in primary mammary tumours.

2016-11-29·Journal of Neuromuscular Diseases

Effect of the Butyrate Prodrug Pivaloyloxymethyl Butyrate (AN9) on a Mouse Model for Spinal Muscular Atrophy

Article

作者: Butchbach, Matthew E. R. ; Edwards, Jonathan D.

Spinal muscular atrophy (SMA) is an early-onset motor neuron disease that leads to loss of muscle function. Butyrate (BA)-based compounds markedly improve the survival and motor phenotype of SMA mice. In this study, we examine the protective effects of the BA prodrug pivaloyloxymethyl butyrate (AN9) on the survival of SMNΔ7 SMA mice. Oral administration of AN9 beginning at PND04 almost doubled the average lifespan of SMNΔ7 SMA mice. AN9 treatment also increased the growth rate of SMNΔ7 SMA mice when compared to vehicle-treated SMNΔ7 SMA mice. In conclusion, BA prodrugs like AN9 have ameliorative effects on SMNΔ7 SMA mice.

100 项与 Pivaloyloxymethyl Butyrate 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05103

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期非小细胞肺癌	临床3期	英国	Titan Pharmaceuticals, Inc.	2003-09-01
晚期非小细胞肺癌	临床3期	美国	Titan Pharmaceuticals, Inc.	2003-09-01
慢性淋巴细胞白血病	临床2期	美国	Titan Pharmaceuticals, Inc.	2004-05-01
小淋巴细胞淋巴瘤	临床2期	美国	Titan Pharmaceuticals, Inc.	2004-05-01
黑色素瘤	临床2期	美国	Titan Pharmaceuticals, Inc.	2004-01-01
晚期非小细胞肺癌	临床2期	印度	Titan Pharmaceuticals, Inc.	2003-09-01
肝癌	临床2期	美国	-	-
肝癌	临床2期	-	Bar-Ilan University	-
肝癌	临床2期	-	Titan Pharmaceuticals, Inc.	-
非小细胞肺癌	临床2期	-	Bar-Ilan University	-