The pharmacology Division of the institute is engaged mainly in anticancer, anti-inflammatory and anti-diabetic drug discovery and development from natural as well as semi-synthetic sources. The division has been working on PI3K-Akt-mTOR signalling, EGFR, DNA methyl transferases, histone methyl transferases and histone deacetylases, the major focus being discovery of target specific novel small molecule modulator(s) from natural products, synthetic and semi-synthetic sources in an attempt to achieve the more potent preventive and chemotherapeutic effects. The division has state of the art facilities for in vitro cytotoxicity studies against human cancer cell lines, in vivo anticancer studies against murine tumor models/human cancer xenograft/orthotropic models and target based in vitro mechanistic studies leading to the discovery of novel anti-cancer chemotherapeutics. On mechanistic side, regulation of tumor invasion, metastasis, epithelial mesenchymal transition (EMT) and wnt /beta-catenin signalling in cancer and stem cell biology by natural products/their semi-synthetic derivatives is the current area of focus. Among inflammatory disorders, the division has programs to develop natural product driven drug candidates for Rheumatoid Arthritis & Inflammatory disorders, diabetes mellitus and obesity. The division is equipped with state of the art GLP standard Animal facility housing number of inbred, outbred and transgenic rodent strains.
- Discovery and development of products/solutions to positively benefit the quality of life of individuals with diseases like cancer, diabetes, rheumatoid arthritis, obesity and pain associated with these conditions.
- Discovery and preclinical development of target based novel molecule(s) for anticancer therapeutics from natural/synthetic/semi-synthetic sources followed by elucidation of mechanism of action in in vitro and in vivo models
- Evaluating the different signaling pathways like PI3K, Akt, mTOR, IGF-R, EGF-R, Wnt/β-Catenin, HDAC, HMT, DNMT in context with cancer biology and drug discovery using proteomic, biochemical and molecular biology approaches
Conducting and supporting basic research, human resource development, imparting training and participation in related cancer research programs at national/international level
- Enzyme inhibition & kinetic constants determination including isoform specific PI3K, Akt, mTOR, IGF-R, EGF-R, HDAC, DNMT, CDK, MMP, HMT, Phosphodiesterase etc; Cytotoxicity assays (MTT, XTT, SRB) against human cancer cell lines representing various cancers
- Cell Migration; Invasion; Clonogenic; Angiogenesis assays like Tube formation, Permeability, Wound Healing, Matrigel Plug assay, Air Sac model, Aortic Ring assay; Gelatin zymography; qPCR; Western; Northern; Luciferase Reporter Gene Assay; Chromatin Immunoprecipitation (ChIP); Histopathology; Immunohistochemistry; Live Cell Imaging; Fluorescence and Immunofluorescence; Confocal Microscopic, Scanning and Transmission Electron Microscopic Studies etc.
- In vivo anticancer studies against murine cancer models such as Ehrlich Ascites Carcinoma; Ehrlich Tumor (Solid); Sarcoma-180 Ascites; Sarcoma-180 (Solid); Methyl Cholanthrere Induced Ascites; L1210 Lymphoid Leukemia; P388 Lymphocytic Leukemia and Human Cancer Xenograft models; In vivo Hollow Fiber Mouse Model; In vivo Preclinical Anticancer Mutagenicity/Anti-mutagenicity Models; etc
- In vitro, in vivo anti-inflammatory activities in cell culture models and rodent models respectively.
- Liver biology
- Skin biology
- Pre-formulation and Drug delivery
- ADME/PK studies
- Toxicity and safety pharmacological studies
Dr. Sreedhar Madishetti
Other Staff List :
Mr. Kuldeep Kumar, Technician (Gr. II)
Mr. Narender Kumar, Tech. Asstt. (Mech.)
Mr. Karan Pal, Technician (Gr. II)
Mr. Satya Bhushan, Technician (Gr. II)
Mrs. Kirti Benjamin, MTS
- Cell Culture Facilities including C02 Incubators and Laminars;
- Cytometers with Cell Sorter
- Gel Documentation System
- Multiplate Detection Reader (UV-Visible/UV, Fluorescence, Luminescence)
- Robotic Liquid Handling System Aided MTS
- Electroblotter; Real Time PCR, 2-D Gel Electrophoretic System.
- FPLC; Deep Freezers (-20°C,-80°C); Refrigerated Centrifuges; Protein, RNA & DNA Electrophoretic Apparatus; Magnetic Stirrer; Millipore Water Purification System; pH Meter; Water Bath; Sonicator; Preparative and Analytical Centrifuges including Ultracentrifuge; High Precision Weighing Balance; Inverted Microscope (Phase Contrast); Fluorescence and Immuno-fluorescence Microscope etc.
- Individually Ventilated Caging Systems; NOD.SCID (Immuno-deficient) Inbred Mice; Luciferase Expressing Human Cancer Cell Lines; IVIS Kinetic In Vivo Optical Imaging System; Inverted Phase Contrast Microscope; UV/Visible Spectrophotometer etc
- HPLC and LC-MS/MS
- Automated biochemical analyzer and Automated Hematology analyzer
|Amit Kumar, Gifty Sawhney, Rakesh Kumar Nagar, Narendra Chauhan, Nidhi Gupta, Anpurna Kaul, Zabeer Ahmed, P.L. Sangwan*, P. Satheesh Kumar, Govind Yadav *(2021)||Evaluation of the immunomodulatory and anti-inflammatory activity of Bakuchiol using RAW 264.7 macrophage cell lines and in animal models stimulated by lipopolysaccharide (LPS)||International Immunopharmacology. 91,https://doi.org/10.1016/j.intimp.2020.107264|
|Kumar V, Mintoo MJ, Mondhe DM, Bharate SB, Vishwakarma RA, Bharate SS||Binary and ternary solid dispersions of an anticancer preclinical lead, IIIM-290: In vitro and in vivo studies.||Int J Pharm 570:118683|
|Dash AK, Nayak D, Hussain N, Mintoo MJ, Bano S, Katoch A, Mondhe DM, Goswami A, Mukherjee D.||Synthesis and Investigation of the Role of Benzopyran Dihydropyrimidinone Hybrids in Cell Proliferation, Migration and Tumor Growth||Anticancer Agents Med Chem. 19(2):276-288|
|Singh G, Hossain MM, Bhat AQ, Ayaz MO, Bano N, Eachkoti R, Dar MJ||Identification of a cross-talk between EGFR and Wnt/beta-catenin signaling pathways in HepG2 liver cancer cells.||Cellular Signalling|
|Bano N, Hossain MM, Bhat AQ, Ayaz MO, Kumari M, Sandhu P, Akhter Y, Dar MJ||Analyzing structural differences between insulin receptor (IR) and IGF1R for designing small molecule allosteric inhibitors of IGF1R as novel anti-cancer agents||Growth Hormone and IGF Research|
|Chander D, Khousla JK, Koul D, Hossain MM, Dar MJ, Chaubey A||Purification and characterization of thermoactive serratiopeptidase from Serratia marcescens AD-W2||AMB Express|
|Singh, U.; Chashoo, G.; Khan, S. U.; Mahajan, P.; Nargotra, A.; Mahajan, G.; Singh, A.; Sharma, A.; Mintoo, M. J.; Guru, S. K.; Aruri, H.; Thatikonda, T.; Sahu, P.; Chibber, P.; Kumar, V.; Mir, S. A.; Bharate, Sonali S. ; Madishetti, S.; Nandi, U.; Singh, G.; Mondhe, D. M.; Bhushan, S.; Malik, F.; Mignani, S.; Vishwakarma , R. A. and Singh., P. P||Design of Novel 3-Pyrimidinylazaindole CDK2/9 Inhibitors with Potent In Vitro and In Vivo Antitumor Efficacy in a Triple-Negative Breast Cancer Model||J. Med. Chem. (2017), 60, 9470−9489|
|Mowkshi Khullar , Ankita Sharma , AbubakarWani , Neha Sharma , Neelam Sharma , B K Chandan , Ajay Kumar , Zabeer Ahmed||Acteoside ameliorates inflammatory responses through NFkB pathway in alcohol induced hepatic damage||International Immunopharmacology; 2019; 69:109-11.|
|Shilpa Gupta,Vidushi Khajuria, Abu bakar Wani, Yedukondalu Nalli, Asha Bhagat, Asif Ali, Zabeer Ahmed||Murrayanine Attenuates Lipo polysaccharide-induced Inflammation and Protects Mice from Sepsis-Associated Organ Failure||Basic & Clinical Pharmacology & Toxicology; 2019 ; 124(4):351-359.|
|Vidushi Khajuria, Shilpa Gupta, Neha Sharma, Harshita Tiwari, Subhash Bhardwaj , PrabhuDutt , Naresh Satti, Amit Nargotra , Asha Bhagat, ZabeerAhmed||Kaempferol-3-o-β-D-glucuronate exhibit potential anti-inflammatory effect in LPS stimulated RAW 264.7 cells and mice model||International Immunopharmacology; 2018; 57:62-71.|
|A. Dogra, S. Bhatt, A. Magotra, A. Sharma, P. Kotwal, A. Gour, P. Wazir, G. Singh, U. Nandi*||Intervention of curcumin on oral pharmacokinetics of daclatasvir in rat: A possible risk for long‐term use.||Phytotherapy Research|
|A. Dogra, A. Gour, S. Bhatt, P. Sharma, A. Sharma, P. Kotwal, P. Wazir, P. Mishra, G. Singh, U. Nandi*||Effect of rutin on pharmacokinetic modulation of diclofenac in rats.||Xenobiotica|
|A.U. Nissar, L. Sharma, M.A. Mudasir, L.A. Nazir, S.A. Umar, P.R. Sharma, R.A. Vishwakarma, S.T. Abdullah*||Chemical chaperone 4-phenyl butyric acid (4PBA) reduces hepatocellular lipid accumulation and lipotoxicity through induction of autophagy.||Journal of Lipid Research.|
|S.T, Abdullah, A. Krishnan, T. Mounajjed, S. Hartono, A. McConico, T. White, N. LeBrasseur, I. Lanza, S. Nair, G. Gores, M. Charlton.||A longitudinal study of whole body, tissue and cellular physiology in a mouse model of fibrosing NASH with high fidelity to the human condition.||American Journal of Physiology-Gastrointestinal and Liver Physiology|
|A. Wani, S.B. Al Rihani, A. Sharma, B. Weadick, R. Govindarajan, S.U. Khan, P.R. Sharma, A. Dogra, U. Nandi, C.N. Reddy, S.S. Bharate, G. Singh, S.B. Bharate, R.A. Vishwakarma, A. Kaddoumi, A. Kumar*||Crocetin promotes clearance of amyloid-β by inducing autophagy via the STK11/LKB1-mediated AMPK pathway.
|A. Wani, M. Gupta, M. Ahmad, A.M. Shah, A. Ul Ahsan, P.H. Qazi, F. Malik, G. Singh, P.R. Sharma, A. Kaddoumi, S.B. Bharate, R.A. Vishwakarma, A. Kumar*||Alborixin clears amyloid-β by inducing autophagy through PTEN mediated inhibition of AKT pathway.
|A. Saneja, D. Nayak, M. Srinivas, A. Kumar, V. Khare, A. Katoch, A. Goswami, R.A. Vishwakarma, S.D. Sawant, P.N. Gupta*||Development and mechanistic insight into enhanced cytotoxic potential of hyaluronic acid conjugated nanoparticles in CD44 overexpressing cancer cells.||European Journal of Pharmaceutical Sciences, 2017, 97, 79-91.|
|R.D. Dubey, R. Klippstein, J. Wang, N. Hodgins, K. Mei, J. Sosabowski, R.C. Hider, V. Abbate, P.N. Gupta, K.T. Al-Jamal
|Novel hyaluronic acid conjugates for dual nuclear imaging and therapy in CD44-expressing tumors in mice in vivo.
|Vishwakarma, Ram Asrey; Bharate, Sandip Bibishan; Bhushan, Shashi; Mondhe, Dilip Manikrao; Jain, Shreyans Kumar; Meena, Samdarshi; Guru, Santosh Kumar; Pathania, Anup Singh; Kumar, Suresh; Behl, Akanksha; Mintoo, Mubashir Javed; Bharate, Sonali Sandip; Joshi, Prashant||Cyclin-dependent kinase inhibition by 5,7-dihydroxy-8-(3-hydroxy-1-methylpiperidin-4-yl)-2-methyl-4H-chromen-4-one analogs||GRANTED
IN Grant No. 322330 / Dt. 04-10-2019
|Bharate SB, Bhushan S, Mohammed S, Guru SK, Bharate SS, Kumar V, Mahajan G, Javed MM, Mondhe DM, Vishwakarma RA||Fused pyrimidines as isoform-selective phosphoinositide-3-kinase-alpha inhibitors and process for preparation thereof||GRANTED
US Patent No. 10696688 / 30-06-2020
|Vishwakarma, Ram; Bharate, Sandip; Kumar, Ajay; Singh, Baljinder; Kumar, Ashok; Bhushan, Shashi; Dar, A.H. Joshi, Prashant; Guru, S.K. Kumar, Suresh; Aashiq, Hussain; Asif, Qazi; Bharate, Sonali; Sharma, P.R.; Saxena, A.K.; Mondhe, D.M.; Mahajan, Girish; Wani, Z.A||10-substituted colchicinoids as potent anticancer agents||GRANTED
US Grant No. 9868695 / Dt. 16-01-2018
|Thatikonda, Thanusha; Kumar, Suresh; Singh, Umed; Mahajan, Priya; Mahajan, Girish; Nargotra, Amit; Malik, Fayaz; Mondhe, Dilip; Vishwakarma, Ram Asrey; Singh, Parvinder Pal||Novel 1,3,5-Triazene based PI3K inhibitors as anticancer agents and a process for the preparation thereof||GRANTED
US Patent No. 9951040 / 24-04-2018
|Singh, Umed; Chashoo, Gousia; Mahajan, Girish; Thatikonda, Thanusha; Mahajan, Priya; Aruri, Hari Prasad; Gudup, Satish Sonbarao; Nargotra, Amit; Mondhe, D. M.; Vishwakarma, Ram||3-pyrimidinyl pyrrolo [2,3-b] pyridine as new anticancer agents and the process for the preparation thereof||PCT/IN20 16/050426 / Dt. 30 November 2016||2016|
|A. Kamal, Y.V.V. Srikanth, M.N.A. Khan, M. Ashraf, I. Sehar, G. Chashoo, P.R. Sharma, A.H. Dar, S. Bhushan, S.K. Singh, D.M. Mondhe and A. K. Saxena.||2-Anilino nicotinyl linked 2-amino benzothiazole conjugates as potential anticancer agents, apoptosis inducers and process for the preparation thereof.||GRANTED
US Grant No. US9029553B2 / Dt. 12.05.2015
|EU Patent no. EP2118065 B1||(Granted :2013|
|Ghulam Nabi Qazi, Subhash Chandra Taneja,Jaswant Singh, Ajit Kumar Saxena, Vijay Kumar Sethi, Bhahwal Ali Shah, Bal Krishan Kapahi, Samar Singh Andotra, Ajay Kumar,Shashi Bhushan, Fayaz Malik, Dilip Manikrao Mondhe, Shanmugavel Muthiah, Surjeet Singh, Monika Verma, Shashank Kumar Singh||Use of semi synthetic analogues of boswellic acids for anticancer activity ,||US Patent US20090298938 A1||(Granted 2009).|
|Qazi ,Ghulam Nabi.; Taneja, Subhash Chandra.;Singh, Jaswant.; Saxena, Ajit Kumar.; Sethi, Vijay Kumar.; Shah, Bhahwal Ali.; Kapahi ,Bal Krishan.;Andotra, Samar Singh.; Kumar, Ajay.; Bhishan, Shashi.; Malik ,Fayaz.; Mondhe, DilipManikarao.; Shanmugavel,Muthiah.; Singh ,Surjeet.; Verma, Monika.; Singh, Shashank Kumar,;||Cytotoxicity And Indusction Of Apoptosis In Cancer Cells By Semi-Synthetic Analogues Of Boswellic Acids For Their Use As Anti-Cancer Agents||(US Patent No US20090298938 A1||(Granted :2009)|
|Qazi ,Ghulam Nabi.; Saxena, Ajit Kumar.; Muthiah ,Shanmugavel.; Mondhe Dilip,Manikrao.; Sharma, Praduman Raj.; Singh, Shashank Kumar.; Utpal,Sanyal.; Mukherjee, Asama.; Hazra ,Suva.; Dutta, Sushanta.||Novel Substituted 1h-Benz[De]Isoquinoline-1,3-Diones As Anticancer Agents .||WO Patent WO2008084496 A1||(Granted :2008)|
|A. Kumar, I.A. Khan, S. Koul, P.L. Sangwan, D.M. Mondhe, U. Nandi, G. Singh, M.K. Tikoo, S. Sharma, A. Wani, S. Rath, S. Singh, M.J. Mintoo, R.A. Vishwakarma||Methods of enhancing bioavailability/ bioefficacy of drugs and pharmaceutical compositions thereof||Filed (IN 201911047260)||2019|
|R.K. Johri, S.T. Abdullah, K. Singh, D.K. Gupta, B.K. Kapahi, D.M. Mondhe, S.M. Jain, O.P. Suri, K.L. Bedi, G.N. Qazi||Herbal hapatocurative agent against CYP450 and free radical mediated drugs toxicity (including-tubercular drugs).||NF53||2002|
|S. Koul, M.V. Reddy, T. Niranjan, J.L. Koul, P.L. Sangwan, S.C. Taneja, I.A. Khan, A. Kumar, N.P. Kalia, S.T. Abdullah, R.K. Johri, S.S. Pagoach, A.K. Tikoo, M.K. Tikoo, A.K. Saxena, S.K. Agrawal, D.M. Mondhe, S.K. Agrawal, B. Purnima, S. Sharma, S. Singh, G.D. Singh, S. Bhusari, G.N. Qazi
|Novel aromatic amides as potentiators of the bioefficacy of drugs||NF0113||2008|
|S.B. Bharate, A. Kumar, J. Bharate, P. Joshi, A. Wani, R. Mudududdla, R. Sharma, R.A. Vishwakarma||Polyprenylated phloroglucinol compounds as potent P- glycoprotein inducers||US Patent Number: US 10,202,326 B2||2019|
|S.B. Bharate, A. Kumar, S. Manda, P. Joshi, S.S. Bharate, A. Wani, S. Sharma, R.A. Vishwakarma||Alkylidene Phosphonate esters as P-glycoprotein inducers|| US Patent number: US 10 377, 781 B2
- Mission Projects
- HCP-38: CSIR-Phytopharma Mission.
- HCP-40: Pan Cancer Mission.
- HCP-23: Sickle Cell Mission (Phase-II).
Major Lab. Projects
- MLP 110007: Preclinical development of small molecule(s) promoting hair regeneration and studying mechanism of hair regeneration.
- MLP 6007:Mouse models for non-invasive detection and quantification of experimental human.
- MLP 110012: Discovery of cannabinoids and their derivatives from Cannabis sativa for the management of chronic disease conditions like rheumatoid arthritis/neuropathic pain.
- MLP 6012: IND Enabling studies.
- MLP-6006: Pre-clinical (PK-PD, safety and toxicity profile) of new bioactive leads and development of new combination drugs for cancer/tuberculosis
- MLP-110004: Development of zinc gluconate-Vitamin C formulation for immunity improvement of coronavirus disease (COVID-19)
- MLP- 6012: Safety pharmacology, toxicology and IND enabling study
- GAP 2168: Solid tumor targeting using homing peptides and plasmonic photothermal technique.
- GAP 2177: Exploration of engineered nanocarrier and modulation of the tumor microenvironment for efficient delivery of anticancer molecule(s) to solid tumor.
- GAP 2143: Isolation, Pharmacopeia standardization and immunomodulation activity of Unani drug Habb-e-suranjan and Habb-e- Asgand.
- GAP 2180: Pharmaceutical development of Ficus semicordata-Ham.ex Sm. As per regulatory guidelines of DCGI.
- GAP 2190: Investigation on the antiobesity activity of Argyreia nervosa, Garcinia species.
- GAP-3105: Development and validation of fermentation based immunomodulatory AYUSH kwath formulation(AYUSH).
- GAP 2194: Selective Spectrum Antibiotic Modulation of the Gut Microbiome in Type 2 Diabetes with Inflammatory Bowel Disease.
- GAP -2166: Discovery of target based novel bioactive natural products from a high altitude plant Hippophae rhamnoides L. (seabuckthorn) and Grewia asiatica (phalsa) for achieving pharmacological and cosmetics effects against ultraviolet radiation induced skin damage (photo-aging/ carcinogenesis)
- GAP-0162: Mechanistic insights in the coexisting pathogenesis of Ethanol and High Cholesterol/High Fat diet -induced End Stage Liver Disease
- GAP-3104: CBD-THC enriched phytopharmaceutical drug for cancer pain management.
- GAP-3107: Development of Boswellia serrata based phytopharmaceutical drug for osteoarthritis.
- GAP-3109: Mechanistic insights in the coexisting pathogenesis of ethanol and high cholesterol/high fat diet-induced end stage liver disease via modulation of adiponectin, insulin & cannabinoid receptors utilizing natural products and their derivatives.
- TLP 110011: Development of Ayurveda based botanical drugs for prophylaxis and management of CIVID-19.
- TLP 110013: Development of Mycobacterium w for COVID-19.