Academic Title:
Assistant Professor
Primary Appointment:
Pharmacology & Physiology
Location:
Rockville MD
Phone (Primary):
240-314-6450
Phone (Secondary):
202-631-3292
Education and Training
Dr. Purushottamachar Puranik received his PhD in Pharmaceutical Chemistry in 2003 from UICT, Mumbai, India. He worked as a process chemist in industry at USV Ltd., India, from 2003 to 2004. He then underwent postdoctoral training at the University of Maryland, Baltimore (UMB) and Thomas Jefferson University, Philadelphia, from 2005 to 2010.
In 2011, he was promoted to a Research Instructor position, and subsequently, in 2012, he returned to UMB/CBT as a Research Associate. He was later promoted to the position of Assistant Professor. Dr. Puranik’s research spans the disciplines of pharmaceutical and biomolecular chemistry. His areas of interest include computer-aided drug design, organic synthesis, and biological evaluation.
Research/Clinical Keywords
Medicinal chemistry, new drug discovery, small molecule synthesis, organic chemistry, design of bio-active molecules, anti-prostate cancer agents, anti-breast cancer agents, chemical process development, steroidal and retinoidal compounds.
Highlighted Publications
- Purushottamachar P, Thomas E, Thankan RS, Njar VCO. Novel deuterated Mnk1/2 protein degrader VNLG-152R analogs: Synthesis, in vitro anti-TNBC activities and pharmacokinetics in mice. Eur. J. Med. Chem. 2022, 238, 114441. PMID35617854
- Purushottamachar P, Thomas E, Thankan RS, Rudchenko V, Haung G, Njar VCO. Large-scale synthesis of galeterone and lead next generation galeterone analog VNPP433-3β. Steroids, 2022, 185, 109062. PMID35690119
- Purushottamachar P, Muragi F, Njar VCO. Improved Procedure for Gram-scale synthesis of Galeterone 3b-imidazole and Galeterone 3b-Pyridine Methoxylate, Potent Androgen Receptor/Mnk degrading Agents. Process. Res. Dev, 2016, 20(9), 1654-1661.
- Purushottamachar P, Kwegyir-Afful AK, et al. Identification of Novel Steroidal Androgen Receptor Degrading Agents Inspired by Galeterone 3β-Imidazole Carbamate. ACS Med. Chem. Lett. 2016, 7(7), 708-13. PMID27437082
- Purushottamachar P, Godbole AM, et al. Systematic structure modifications of multi-target prostate cancer clinical candidate galeterone to produce novel androgen receptor down-regulating agents as an approach to treatment of advanced prostate cancer. J. Med. Chem. 2013, 56(12), 4880-98. PMID23713567
Additional Publication Citations
- Thankan RS, Thomas E, Weldemariam MM, Purushottamachar P, Huange W, et al., Thermal proteome profiling and proteome analysis uing high-definition mass spectrometry demonstrated modulation of cholesterol biosynthesis by next-generation galeterone analog VNPP433-3b in castration resistant prostate cancer. Mol Oncology, 2025, 19(8), 1878-2309. PMID40007440
- Thankan RS, Thomas E, Purushottamachar P, Weber DJ, et al., VNLG-152 and its deuterated analogs potentially inhibit/repress triple/quadruple negative breast cancer of diverse racial origins in vitro and in vivo by upregulating E3 Ligase Synoviolin 1 (SYVN1) and inducing proteasomal degradation of MNK1/2. Front Onc, 2023, 1240996. PMID37766871
- Thankan RS, Thomas E, Purushottamachar P, Weber DJ, Njar VCO. Salinization dramatically enhance the anti-prostate cancer efficacies of AR/AR-V7 and Mnk1/2 molecular glue degraders, Galeterone and VNPP433-3B which outperform docetaxel and enzalutamide in CRPC CWR22Rv1 xenograft mouse model. Bioorg Chem, 2023, 106700. PMID37392599
- Thomas E, Thankan RS, Purushottamachar P, Guo J, Parise RA, Beumer JH, Njar VCO. Murine toxicology and pharmacokinetics of lead next generation glaterone analog, VNPP433-3β. Steroids, 2023, 192, 109184. PMID36702363
- Rorke EA, Adhikary G, Szmacinski H, Lakowicz JR, Weber DJ, Godoy-Ruiz R, Puranik P, Keillor JW, Gates EWJ, Eckert RL. Sulforaphane covalently interacts with the transglutaminase 2 cancer maintenance protein to alter its structure and suppress its activity. Mol Carcinog. 2021 Oct 5. doi: 10.1002/mc.23356. Epub ahead of print. PMID: 34610184.
- Kwegyir-Afful AK, Ramalingam S, Ramamurthy VP, Purushottamachar P, et al. Galeterone and the next generation galeterone analogs, VNPP414 and VNPP433-3β exert potent therapeutic effects in castration-/drug-resistant prostate cancer preclinical models in vitro and in vivo. Cancers, 2019, 11 (11), 1637. PMID31653008
- Thomas E, Thankan RS, Purushottamachar P, Weber DJ, Njar VCO. Targeted degradation of Androgen Receptor by VNPP433-3 β in castration resistant prostate cancer cells implicates interaction with E3 ligase MDM2 resulting in ubiquitin-proteasomal degradation. Cancers, 2023, 15(4), 1198. PMID36831540
- Purushottamachar P, Njar VCO. A new simple and high-yield synthesis of 5a-dihydrotestosterone (DHT), a potent androgen receptor agonist. Steroids, 2012, 77, 1530-1534. PMID23055354
- Godbole AM, Purushottamachar P, Martin MS, Daskalakis C, Njar VCO. Autophagy inhibition synergistically enhances anti-cancer efficacy of RAMBA, VN/12-1 against SKBR-3 Cells and murine xenografts. Mol. Cancer Ther., 2012, 11, 898-908. PMID22580781
- Purushottamachar P. Novel approach: androgen receptor down-regulating agents for the treatment of all stages of prostate cancer disease. Biochem & Pharmacol, 2012, 1 (3):e115.
- Purushottamachar P, Patel JB, Clement OO, Njar VCO. First chemical feature-based pharmacophore modeling of potent retinoidal retinoic acid metabolism blocking agents (RAMABAs): identification of novel RAMBA scaffolds. Eur. J. Med. Chem., 2012, 47(1), 412-423. PMID22130607
- Purushottamachar P, Khandelwal A, et al. Potent anti-prostate cancer agents derived from a novel androgen receptor down-regulating Agent. Bioorg. Med. Chem., 2008, 16 (7), 3519-3529. PMID18316193
- Purushottamachar P, Khandelwal A, et al. First pharmacophore-based identification of androgen receptor down-regulating agents: discovery of potent anti-prostate cancer agents. Bioorg. Med. Chem., 2007, 15 (10), 3413-3421. PMID17383188
- Purushottamachar P, Kulkarni VM, 3D-QSAR of N-myristoyltransferase (Nmt) antifungal agents: CoMFA and CoMSIA study. Bioorg. Med. Chem., 2003, 11, 3487-3497. PMID12878142
- Udupi, R. H, Purushottamachar P. Synthesis and biological screening of new s-triazolo-thiadiazines and thiadiazoles. Ind. J. Het. Chem., 2000, 9, 283-286.
Research Interests
The focus of Dr. Puranik’s research is the rational design, synthesis, and evaluation of novel, patentable small molecules with the potential to prevent and/or treat prostate and breast cancers. He is also interested in understanding the mechanisms underlying the anticancer actions of these novel agents.
His research lies at the interface of medicinal chemistry and pharmacology/oncology, with an emphasis on elucidating the mechanisms of action of novel androgen receptor down-regulating agents (ARDAs), androgen synthesis inhibitors, and retinoic acid metabolism blocking agents (RAMBAs). These targets are well-validated in drug discovery and development for prostate and breast cancer and continue to be an important focus in modern drug discovery.
In his research, Dr. Puranik employs modern drug discovery tools such as structure-based drug design (SBDD) and analog-based drug design approaches, including pharmacophore modeling and 3D-QSAR, for the rational design and lead optimization of novel agents. He also carries out the organic synthesis of small molecules and their biological evaluation to achieve his medicinal chemistry and pharmacology research goals.