Aleem Gangjee, Ph.D.

Synthetic medicinal chemistry, computer-assisted drug design, inhibitors of folate metabolizing enzymes, receptor tyrosine kinase inhibitors, antimitotic agents, antitumor agents, antiopportunistic infection agents, nucleosides, heterocyclic chemistry and stereochemistry.

Undergraduate Courses Taught:
232 Basic Pharmacology (University of Pittsburgh, 1983)
309 Biochemistry and Nutrition
310 Analysis of Drug Substances
313 Medicinal Chemistry & Natural Products
314 Medicinal Chemistry & Natural Products
352 Foundations of Pharmacology and Medicinal Chemistry
421 Medicinal Chemistry
427 Biomedical Sciences/Therapeutics VI: Pulmonary, Oncology and Hematology Module
429 Biomedical Sciences and Therapeutics VIII

Graduate Courses Taught:
522 Spectral Methods
523 Advanced Medicinal Chemistry I
524 Advanced Medicinal Chemistry II
623 Selected Topics in Medicinal Chemistry
671 Chemistry of Heterocyclic Compounds
527 Advanced Medicinal Chemistry

Ranked first in the graduating M.S. Class of 1971, Organic Chemistry, Indian Institute of Technology.

International Student Scholarship, University of Iowa, 1971-75.

Research Assistantship, Graduate College, University of Iowa, 1971-75.

Award for Outstanding Academic Achievement Graduate College, University of Iowa, 1973.

Phi Lambda Upsilon, Chemistry Honor Society, 1975.

Postdoctoral Trainee Fellowship National Cancer Institute training grant at SUNY, Buffalo, 1976-1979.

The American Men and Women of Science, 1979.

Rho Chi, Pharmacy Honor Society, 1980.

The Society of Sigma XI, 1981.

Starter Grant, Faculty Research and Scholarship Award, Duquesne University, April 1982.

The New York Academy of Science, 1982.

President, Duquesne Sigma Xi Club, 1983.

Runner-up Duquesne Man of the Year, 1985-86.

Commencement Speaker, Pharmacy Class of 1988.

Duquesne University Presidential Award for Faculty Excellence in Scholarship, 1988.

School of Pharmacy Teacher of the Year Award, 1988.

Shannon Award, NIH, 1991.

Who's Who in American Education, 1992.

National Institutes of Health (NIH) consultant.

Duquesne University School of Pharmacy Award for Excellence in Research, 1995.

Who's Who in Medicine and Healthcare, 1996.

Elected to the American Association for Cancer Research, 1996.

National Institutes of Health, BNP-1 Special Emphasis Pane Study Sectionl, 1996.

Duquesne University School of Pharmacy Award for Excellence in Teaching, 1997.

Duquesne University Presidential Award for Faculty Excellence in Teaching, 1997.

Awarded 29 US patents.

World Health Organization invited participant in collaborative research, 1998.

Granted the title of Mylan School of Pharmacy Distinguished Professor, 1998.

NIH National Cancer Institute Study Section Experimental Therapeutics I, 1999-2003.

Chosen as a N.C.P.A. Member's Favorite Professor, 2000.

Editorial Advisory Board Member, Current Medicinal Chemistry, Anti-Cancer Agents, 2001-present.

Ad-Hoc Member: National Institutes of Health, Center for Scientific Review, AIDS and Related Research, 2002-2003.

Ad-Hoc Member: National Institutes of Health, Center for Scientific Review, AIDS and

AIDS Related Research Integrated Review Group (AARR), AIDS and AIDS Related Research Study Section, 2003-2004.

Ad-Hoc Member: National Institutes of Health, Center for Scientific Review, Oncologic

Sciences Integrated Review Group, Drug Discovery & Molecular Pharmacology (DMP) Study Section, 2003-2004.

Editorial Board of Medicinal Chemistry Reviews - Online, 2004-2006.

Member of The Honor Society of Phi Kappa Phi, 2007.

Recipient of the President's Award for Faculty Excellence in Scholarship, September 2008.

Member: Editorial Advisory Board, Journal of Medicinal Chemistry, 2008-2012.

Received the President's Award for Faculty Excellence in Scholarship, Sept. 2008.

Adrian Van Kaam, C.S.Sp., Endowed Chair in Scholarly Excellence, 2010-2015.

Chairperson: National Institutes of Health, Center for Scientific Review Special Emphasis Panel, ZRG1 OTC-K (04) Cancer Therapeutics Study Section; Feb. 17, 2011.

2012 Avis Distinguished visiting Professor at the College of Pharmacy, University of Tennessee, Memphis, TN, April 23-24, 2012.

Recipient of the 2012 Research Achievement Award in Drug Discovery and Development Interface, American Association of Pharmaceutical Scientists, (AAPS), Oct. 14, 2012.

Antitumor Antimitotics That Reverse Tumor Resistance NIH, National Cancer Institute (NCI) Five years: Feb. 24, 2006 -- Jan. 31, 2011.

Novel, P. jirovecii Specific Antipneumocystis Agents NIH, National Institute of Allergy and Infectious Diseases (NIAID) five years: May 15, 2006 to Apr. 30, 2011.

Alpha Folate Receptor Mediated GARFTase Inhibitors as Selective Antitumor Agents
NIH, National Cancer Institute Five years: Sept. 26, 2006 to July 31, 2012.  Single Agents With Designed Combination Chemotherapy Potential National Institutes of Health, National Cancer Institute (NIH/NCI) American Recovery and Reinvestment Act of 2009 Two years: June 1, 2009 to May 31, 2012.

Duquesne University Five year appointment 2010 - 2015: Adrian Van Kaam, C.S.Sp. Endowed Chair for Scholarly Excellence. Awarded: $15,000/per year ($75,000 total).

Discovery of Novel PCFT-Targeted Agents. National Institutes of Health, National Cancer Institute (NCI). March 1, 2011 to Feb. 28, 2016. Larry Matherly and Aleem Gangjee. Total award $2,296,601.

Water Soluble Antimitotics That Circumvent Tumor Resistance. National Institutes of Health, National Cancer Institute (NCI) June 1, 2011 to March 31, 2016. Aleem Gangjee and Susan Mooberry. Total award: $1,567,135.

Pneumocystis jirovecii Targeted Antiopportunistic Agents. National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID), 02/01/2012 - 01/31/2017. Principal Investigator. $1,903,735

Purine Synthesis Inhibitors with Selective Folate Receptor Tumor Transport. National Institutes of Health, National Cancer Institute (NCI), 02/05/2013 - 01/31/2016, Co-Principal Investigator Aleem Gangjee, Dr. Larry Matherly and Dr. Charles Dann III , $1,563,106.

Partial list:

Synthesis and Biological Activity of 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Regioisomers as Inhibitors of de Novo Purine Biosynthesis with Selectivity for Cellular Uptake by High Affinity Folate Receptors and the Proton-Coupled Folate Transporter Over the Reduced Folate Carrier. J. Med. Chem., 2012, 55, 1758-1770. PubMed 22243528; NIHMSID 355201; doi: 10.1021/jm201688n.

Gangjee, A.; Zaware, N.; Raghavan, S.; Yang, J.; Thorpe, J. E. and Ihnat, M. A. N^₄-(3-Bromophenyl)-7-(substituted Benzyl) Pyrrolo[2,3-d]pyrimidines as Potent Multiple Receptor Tyrosine Kinase Inhibitors: Design, Synthesis and in vivo Evaluation. Bioorg, Med. Chem., 2012, 20, 2444-2454. NIHMSID 361890. doi: 10.1016/j.bmc.2012.01.029. https://www.nihms.nih.gov/pmc/articlerender.fcgi?artid=361890.

Gangjee, A.; Zhao, Y.; Inhat, M. A.; Thorpe, J. E.; Bailey-Downs, L. C. and Kisliuk, R. L. Novel Tricyclic Indeno[2,3-d]pyrimidines with Dual Antiangiogenic and Cytotoxic Activities as Potent Antitumor Agents. Bioorg. Med. Chem., 2012, 20, 4217-4225. http://dx.doi.org/10.1016/j.bmc.2012.05.068. https://www.nihms.nih.gov/pmc/picrender.fcgi?artid=383141&blobtype=pdf.

Gangjee, A.; Pavana, R. K.; Li, W.; Hamel, E.; Westbrook, C. and Mooberry, S. L. Novel Water-Soluble Substituted Pyrrolo[3,2-d]pyrimidines: Design, Synthesis and Biological Evaluation as Antitubulin Antitumor Agents. Pharm. Res., 2012, 29, 3033-3039. doi: 10.1007/s11095-012-0816-3; NIHMS395167.

Desmoulin, S. K.; Wang. L.; Polin, L.; White. K.; Kushner, J.; Stout, M.; Hou, Z.; Cherian, C.; Gangjee, A. and Matherly, L. H. Functional Loss of the Reduced Folate Carrier Enhances the Antitumor Activities of Novel Antifolates with Selective Uptake by the Proton-Coupled Folate Transporter. Mol. Pharmacol. Fast Forward, June 2012, 82, 591-600, doi:10.1124/mol.112.079004. (Oct 2012).Menter, A.; Thrash, B.; Cherian, C.; Matherly, L. H.; Wang, L.; Gangjee, A.; Morgan, J. R.; Maeda, D. Y.; Schuler, A. D.; Kahn, S. J. and Zebala, J. A. Intestinal Transport of Aminopterin Enantiomers in Dogs and Humans with Psoriasis is Stereoselective: Evidence for a Mechanism Involving the Proton-Coupled Folate Transporter. J. Pharmacol. and Experim. Therap., 2012, 342, 696-708. http://dx.doi.org/10.1124/jpet.112.195479.

Desmoulin, S. K.; Hou, Z.; Gangjee, A. and Matherly, L. H. The Human Proton-Coupled Folate Transporter. Biology and Therapeutic Applications to Cancer. Cancer Biol. & Therapy, 2012, 13, 1355-1373. http://;dx.doi.org/10.4161/cbt.22020.

Gangjee, A.; Kurup, S.; Ihnat, M. A.; Thorpe, J. E. and Disch, B. N₄-Aryl-6-substitutedphenylmehtyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as Receptor Tyrosine Kinase Inhibitors. Bioorg. Med. Chem., 2012, 20, 910-914. doi: 10.1016/j.bmc.2011.11.058.

Gangjee, A.; Zaware, N.; Devambatla, R. K. V.; Raghavan, S.; Westbrook, C. D.; Dybdal-Hargreaves, N. F.; Hamel, E. and Mooberry, S. L. Synthesis of N^₄-(substituted phenyl)-N⁴-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and Identification of New Microtubule Disrupting Compounds That Are Effective Against Multidrug Resistant Cells. Bioorg. Med. Chem., 2013, 21, 891-902. http://dx.doi.org/10.1016/j.bmc.2013.12.010. https://www.nihms.nih.gov/pmc/articlerender.fcgi?artid=437554.

Gangjee, A.; Kurup, S. and Smith, C. D. Synthesis of 5,7-Disubstituted-4-methyl-7H-pyrrolo[2,3-d]pyrimidin-2-amines as Microtubule Inhibitors. Bioorg. Med. Chem., 2013, 21, 1180-1189. http://dx.doi.org/10.1016/j.bmc.2012.12.029. (Feb 2013).

Gangjee, A.; Namjoshi, O. A.; Yu, J.; Ihnat, M. A.; Thorpe, J. E. and Bailey-Downs, L. C. N²-Trimethylacetyl Substituted and Unsubstituted-N⁴-phenylsubstituted-6-(2-pyridin-2-ylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines: Design, Cellular Receptor Tyrosine Kinase Inhibitory Activities and in vivo Evaluation as Antiangiogenic, Antimetastatic and Antitumor Agents. Bioorg. Med. Chem., 2013, 21, 1312-1323. http://dx.doi.org/10.1016/j.bmc.2012.12.045. (Feb 2013).

Gangjee, A.; Kurup, S.; Ihnat, M. A.; Thorpe, J. E. and Disch, B. N⁴-Aryl-6-substitutedphenylmethyl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as Receptor Tyrosine Kinase Inhibitors. Bioorg. Med. Chem., 2012, 20, 910-914. NIHMSID 346944; PubMed 22204741. http://www.sciencedirect.com/science/article/pii/S0968089611009941.

Gangjee, A.; Namjoshi, O. A.; Keller, S. N. and Smith, C. D. 2-Amino-4-methyl-5-phenylethyl substituted-7-N-benzyl-pyrrolo[2,3-d]pyrimidines as Novel Antitumor Antimitotic Agents that Also Reverse Tumor Resistance. Bioorg. & Med. Chem., 2011, 19, 4355-4365.

Zhang, X.; Zhou, Z.; Kisliuk, R. L.; Piraino, J.; Cody, V. and Gangjee, A. Design, Synthesis, Biological Evaluation and X-ray Crystal Structure of Novel Classical 6,5,6-tricyclic Benzo[4,5]thieno[2,3-d]pyrimidines as Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors. Bioorg. & Med. Chem., 2011, 19, 3585-3594.

Matherly, L. H. and Gangjee, A. Discovery of Novel Antifolate Inhibitors of de Novo Purine Nucleotide Biosynthesis with Selectivity for High Affinity Folate Receptors and the Proton-Coupled Folate Transporter Over the Reduced Folate Carrier for Cellular Entry. In Targeted Drug Strategies for Cancer and Inflammation, A. L. Jackman, C. Leamon, Eds., Springer, New York, 2011. 110-134.

Wang, L.; Desmoulin, S. K.; Cherian, C.; Polin, L.; White, K.; Kushner, J.; Fulterer, A.; Chang, M-H.; Mitchell-Ryan, S.; Stout, M.; Romero, M. F.; Hou, Z.; Matherly, L. H. and Gangjee, A. Synthesis, Biological and Antitumor Activity of a Highly Potent 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Antifolate Inhibitor with Proton-Coupled Folate Transporter and Folate Receptor Selectivity Over the Reduced Folate Carrier That Inhibits beta-Glycinamide Ribonucleotide Formyltransferase. J. Med. Chem., 2011, 54, 7150-7164. PubMed 21879757; NIHMSID 328244. https://www.nihms.nih.gov/pmc/articlerender.fcgi?artid=328244.

Gangjee, A.; Zhao, Y.; Hamel, E.; Westbrook, C. and Mooberry, S. L. Synthesis and Biological Activities of (R)- and (S)-N-(4-methoxyphenyl)-N,2,6-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-aminium Chloride as Potent Cytotoxic Antitubulin Agents. J. Med. Chem., 2011, 54, 6151-6155. DOI 10.1021/jm2007722, PubMed 21786793, NIHMSID 314812.

Desmoulin, S. K.; Wang, L.; Hales, E.; Polin, L.; White, K.; Kushner, J.; Stout, M.; Hou, Z.; Cherian, C.; Gangjee, A. and Matherly, L. H. Therapeutic Targeting of a Novel 6-Substituted Pyrrolo[2,3-d]pyrimidine Thienoyl Antifolate to Human Solid Tumors Based on Selective Uptake by the Proton-Coupled Folate Transporter. Mol. Pharmacol. Fast Forward, Sept. 22, 2011, doi: 10.1124/mol.111.073833.

Gangjee, A.; Namjoshi, O. A., Ihnat, M. A. and Buchanan, A. The Contribution of a 2-Amino Group on Receptor Tyrosine Kinase Inhibition and Antiangiogenic Activity in 4-Anilinosbustituted Pyrrolo[2,3-d]pyrimidines. Bioorg. & Med. Chem. Ltrs., 2010, 20, 3177-3181. NIHMSID 192103. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866134/?tool=nihms.

Gangjee, A.; Zhao, Y.; Raghavan, S.; Ihnat, M. A. and Disch, B. C. Design, Synthesis and Evaluation of 2-Amino-4-m-bromoanilino-6-arylmethyl-7H-pyrrolo[2,3-d]pyrimidines as Tyrosine Kinase Inhibitors and Antiangiogenic Agents. Bioorg. & Med. Chem., 2010, 18, 5261-5273. NIHMSID 210323; PubMed 20558072; Publ. ID BMC8418.

Gangjee, A.; Kurup, S.; Ihnat, M. A.; Thorpe, J. E. and Shenoy, S. S. Synthesis and Biological Activity of N4-Phenylsubstituted-6-(2,4-dichlorophenylmethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4- diamines as Vascular Endothelial Growth Factor Receptor-2 Inhibitors and Antiangiogenic and Antitumor Agents. Bioorg. & Med Chem., 2010, 18, 3575-3587. NIHMSID 193243, PubMed 20403700. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2868963/?tool=nihms.

Desmoulin, S. K.; Wang, Y.; Wu, J.; Stout, M.; Hou, Z.; Fulterer, A.; Chang, M-H.; Romero, M. F.; Cherian, C.; Gangjee, A. and Matherly, L. H. Targeting the Proton-Coupled Folate Transporter for Selective Delivery of 6-Substituted Pyrrolo[2,3-d]pyrimidine Antifolate Inhibitors of de novo Purine Biosynthesis in the Chemotherapy of Solid Tumors. Mol. Pharmacol., 2010, 78, 577.587. DOI: 10.1124/mol.110.065896.

Gangjee, A.; Zhao, Y.; Lin, L.; Raghavan, S.; Roberts, E. G.; Risinger, A. L.; Hamel, E. and Mooberry, S. L. Synthesis and Discovery of Water Soluble Microtubule Targeting Agents that Bind to the Colchicine Site on Tubulin and Circumvent Pgp Mediated Resistance. J. Med. Chem., 2010, 53, 8116-8128. http://pubs.acs.org/doi/pdfplus/10.1021/jm101010n; http://pubs.acs.org/doi/suppl/10.1021/jm101010n/suppl_file/jm101010n_si_001.pdf; NIHMSID 248371; Publ. ID. jm101010n; PubMed # 20973488; https://www.nihms.nih.gov/pmc/articlerender.fcgi?artid=248371.

Cody, V.; Piraino, J.; Pace, J.; Li, W. and Gangjee, A. Preferential Selection of Isomer Binding From Chiral Mixutures: Alternate Binding Modes Observed for the E- and Z-isomers of a Series of 5-Substitited 2,4-Diamino[2,3-d]pyrimidines as Ternary Complexes with NADPH and Human Dihydrofolate Reductase. Acta. Crystal. D., 2010, D66, 1271-1277.

Gangjee, A.; Zaware, N.; Raghavan, S.; Ihnat, M.; Shenoy, S. and Kisliuk, R. L. Single Agents with Designed Combination Chemotherapy Potential: Synthesis and Evaluation of Substituted Pyrimido[4,5-b]indoles as Receptor Tyrosine Kinase and Thymidylate Synthase Inhibitors and as Antitumor Agents. J. Med. Chem., 2010, 53, 1563-1578. NIHMSID 173160. PMID 20092323. http://pubs.acs.org/doi/pdf/10.1021/jm9011142.

Gangjee, A.; Lin, X.; Biondo, L. and Queener, S. F. CoMFA Analysis of tgDHFR and rlDHFR Based on Antifolates with 6-5 Fused Ring System Using the All-Orientation Search (AOS) Routine and a Modified Cross-Validated r²-Guided Region Selection (q²-GRS) Routine and Its Initial Application. Bioorg. & Med. Chem., 2010, 18, 1684-1701. DOI: 10.1016/j.bmc.2009.12.066. PMID 20117005. https://www.nihms.nih.gov/pmc/articlerender.fcgi?artid=176663.

Wang, L.; Cherian, C.; Desmoulin, S. K.; Polin, L.; Deng, Y.; Wu. J.; Hou, Z.; White, K.; Kushner, J.; Matherly, L. H. and Gangjee, A. Synthesis and Antitumor Activity of a Novel Series of 6-substituted pyrrolo[2,3-d]pyrimidine Thienoyl Antifolate Inhibitors of Purine Biosynthesis with Selectivity for High Affinity Folate Receptors and the Proton-coupled Folate Transporter over the Reduced Folate Carrier for Cellular Entry. J. Med. Chem., 2010, 53, 1306-1318. DOI: 10.1021/jm9015729. NIHMSID 171980. PMID 20085328.

Gangjee, A.; Jain, H. D.; Phan, J.; Guo, X.; Queener, S. F.; Kisliuk, R. L. 2,4-Diamino-5-methyl-6-substituted Arylthio-furo[2,3-d]pyrimidines as Novel Classical and Nonclassical Antifolates as Potential Dual Thymidylate Synthase and Dihydrofolate Reductase Inhibitors. Bioorg. & Med. Chem., 2010, 18, 953-961. NIHMSID 167667. PMID 20056546.