Delving into the Latest Updates on Piramal Phytocare Ltd. with Synapse

Overview

Basic Info

Introduction

Piramal Phytocare Ltd. is a pharmaceutical company that specializes in creating healthcare solutions from natural sources. Established in 2001, Piramal Phytocare Ltd. is headquartered in Mumbai, India.

Tags

Immune System Diseases

Respiratory Diseases

Neoplasms

Herbal medicine

Small molecule drug

Disease domain score

A glimpse into the focused therapeutic areas

Technology Platform

Most used technologies in drug development

Targets

Most frequently developed targets

Disease Domain	Count

Immune System Diseases	1
Neoplasms	1

Top 5 Drug Type	Count

Herbal medicine	1
Small molecule drug	1

Top 5 Target	Count

ALK1 x PI3K family x mTOR	1

Aggregation/misfolding of α-synuclein and βA4 proteins cause neuronal cell death (NCD) associated with Parkinson's and Alzheimer's disease. It has been suggested that a heat shock protein-90 (Hsp90) inhibitor can prevent NCD by activating the heat shock transcription factor-1 which, in turn, upregulates molecular chaperones such as Hsp70 that targets aggregated/misfolded proteins for refolding/degradation. We have isolated radicicol, an Hsp90 inhibitor, from a fungus occurring in the crevices of marble rocks of Central India. Radicicol, which was found to be a strong antioxidant, was tested for its ability to rescue yeast cells from death induced by expression of wild-type α-synuclein, its more toxic A53T mutant, and βA4. It effectively overcomes wild-type/mutant α-synuclein mediated yeast cell death, concomitantly diminishes ROS levels, reverses mitochondrial dysfunction and prevents nuclear DNA-fragmentation, a hallmark of apoptosis. Surprisingly however, radicicol is unable to rescue yeast cells from death triggered by expression of secreted βA4. Moreover, although radicicol acts as an antioxidant it fails to prevent yeast cell death inflicted by the proapoptotic protein, Bax. Our results indicate that radicicol specifically targets aggregated/misfolded α-synuclein's toxicity and opens up the possibility of using multiple yeast assays to screen natural product libraries for compounds that would unambiguously target α-synuclein aggregation/misfolding.

15 Jul 2016·Cancer Research

Abstract 1727: Quinomycin A inhibits pancreatic cancer growth and affects stem cell viability by inhibiting oncogenic YAP1 function

Author: Anant, Shrikant ; Ponnurangam, Sivapriya ; Ramamoorthy, Prabhu ; Fnu, Gaurav ; Weir, Scott J. ; Umar, Shahid ; Subramaniam, Dharmalingam ; Balakrishnan, Arun ; Dhar, Animesh ; Jensen, Roy A. ; Tawfik, Ossama W.

AbstractBackground: Pancreatic cancer (PCa) remains a leading cause of death in the United States. Cancer stem cells (CSC) are responsible for tumor behavior, and therapeutic resistance. Quinomycin (Qui) is an orally administered quinoxaline antibiotic that bifunctionally intercalates with double stranded DNA. As a first step for repurposing this drug, we determined whether Qui affects PCa growth, and if so whether this is by suppressing stem cells.Method: Growth and apoptosis of PCa lines (MiaPaCa-2, PanC-1, BxPC-3) and normal ductal epithelial cells (HPNE) was measured by hexosaminidase and clonogenicity, and caspase 3/7 assays, respectively. Pancosphere formation and FACS sorting were used to identify effects on stem cells. For in vivo, MiaPaCa-2 xenografts were developed in the flanks of nude mice. Immunohistochemistry was performed for stem cell markers and Hippo signaling proteins.Results: Qui demonstrated a dose- and time-dependent inhibition of proliferation and colony formation in all three PCa lines but not HPNE cells. Qui induced PCa cells to undergo apoptosis. It also significantly reduced the number and size of pancospheres, and flow cytometry and western blot analyses confirmed that Qui suppressed PCa stem cell marker proteins DCLK1, CD44, CD24 and EPCAM. We next determined whether Hippo signaling pathway is affected. For this, we tested the effect of Qui on Hippo signaling pathway, which is an active pathway in CSCs including in PCa. The key effector protein, YAP1 has been shown to be oncogenic in many cancer types. In the canonical Hippo signaling pathway, YAP1 function is inhibited. When YAP1 is phosphorylated at Ser127 by the action of upstream Mst1/2 and Lats1/2 kinases, it is sequestered in the cytoplasm, and therefore no induction of downstream gene expression. Qui significantly decreased the phosphorylation oncogenic YAP1. Furthermore, Qui inhibited the expression of YAP interacting proteins TEAD1, TEAD2, and TEAD4. On the other hand, ectopic expression of the TEAD1 partially rescued the cells from Qui-mediated growth suppression. To determine the effect of Qui on tumor growth in vivo, mice carrying MiaPaCa-2 tumor xenografts were administered the compound intraperitoneally (20 μg/kg bw) every day for 21 days. Qui treatment significantly suppressed tumor xenograft growth, with notably lower tumor volume and weight. Western blot and immunohistochemistry analyses demonstrated significant inhibition in the expression of CSC marker proteins, oncogenic YAP1 phosphorylation and YAP1 interacting proteins TEAD1 in the Qui-treated xenograft tissues.Conclusion: Together, these data suggest that Qui suppresses PCa growth that targets that targets stem cells by inhibiting oncogenic YAP1 in Hippo signaling pathway.Citation Format: Dharmalingam Subramaniam, Sivapriya Ponnurangam, Gaurav Fnu, Prabhu Ramamoorthy, Animesh Dhar, Ossama W. Tawfik, Shahid Umar, Scott J. Weir, Roy A. Jensen, Arun Balakrishnan, Shrikant Anant. Quinomycin A inhibits pancreatic cancer growth and affects stem cell viability by inhibiting oncogenic YAP1 function. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1727.

01 Dec 2015·Nutrition & MetabolismQ3 · MEDICINE

A novel anti-inflammatory natural product from Sphaeranthus indicus inhibits expression of VCAM1 and ICAM1, and slows atherosclerosis progression independent of lipid changes

Q3 · MEDICINE

ArticleOA

Author: Mistry, Sapna ; Sharma, Somesh ; Srivastava, Rai Ajit K

A large body of evidence suggests that atherosclerosis is an inflammatory disease, in which cytokines and growth factors play a major role in disease progression. The methanolic extracts of Sphaeranthus indicus as well as its active ingredient, 7-hydroxy frullanoide (7-HF), are shown to suppress LPS-induced cytokine production from mononuclear cells, and inhibit the expression of VCAM1, ICAM1 and E-selectin by TNF-α- stimulated HUVECs in a concentration-dependent manner. We tested the hypothesis that the inhibition of cytokines and adhesion molecules should attenuate the progression of atherosclerosis, independent of changes in the lipid profile. Studies were carried out in two animal models: a high fat-fed LDLr(-/-) mouse and a high fat-fed hyperlipidemic hamster. Methanolic extract of S. indicus was dosed to hyperlipidemic LDLr(-/-) at 100 and 300 mg (equivalent to 20 and 60 mg 7-HF)/kg body weight/ day for 8 weeks, and plasma lipids as well as aortic lesion area were quantitated. Hyperlipidemic hamsters were treated with one dose of 200 mg/kg/day. S. indicus extract treatment did not alter the lipid profile in both animal models, but reduced aortic lesion area in LDLr(-/-) mice and hyperlipidemic hamsters by 22 % and 45 %, respectively. Fenofibrate, included as a reference agent, decreased aortic lesions by 26 % in LDLr (-/-) mice and 84 % in hyperlipidemic hamsters, respectively, which was driven by massive reductions in proatherogenic lipoproteins. The lipid-independent anti-atherosclerotic activity of S. indicus was associated with the reductions in the circulating levels of MCP-1, TNF-α, and IL-6 via phosphorylation and degradation of IkB-α that prevents translocation of NF-kB in the nucleus to induce proinflammatory cytokines. Our findings demonstrate that anti-inflammatory agents that lower pro-inflammatory proteins inhibit the progression of atherosclerosis. The methanolic extract of S. inducus, currently being used to treat psoriasis, offer promise to benefit individuals who have high circulating pro-inflammatory cytokines, and predisposed to coronary artery disease.

100 Deals associated with Piramal Phytocare Ltd.

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100 Translational Medicine associated with Piramal Phytocare Ltd.

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Pipeline

Pipeline Snapshot as of 22 Nov 2024

The statistics for drugs in the Pipeline is the current organization and its subsidiaries are counted as organizations,Early Phase 1 is incorporated into Phase 1, Phase 1/2 is incorporated into phase 2, and phase 2/3 is incorporated into phase 3

Preclinical

1

Approved

Other

12

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Current Projects

Drug(Targets)	Indications	Global Highest Phase

Tinefcon	Plaque psoriasis More	Approved
Panulisib ( ALK1 x PI3K family x mTOR )	KRAS mutant Non-small Cell Lung Cancer More	Preclinical
[18F]FEMPA ( TSPO )	Diagnostic agents More	Discontinued
NPB-001-056 ( Bcr-Abl )	Philadelphia chromosome positive chronic myelogenous leukemia More	Discontinued
PP-9706642	Herpes Simplex More	Discontinued