Aleem Gangjee

Distinguished Professor
School of Pharmacy & Graduate School of Pharmaceutical Sciences
Adrian Van Kaam Chair in Scholarly Excellence

451 Mellon Hall
Phone: 412.396.6070
gangjee@duq.edu

Education:

Ph.D., Medicinal Chemistry, University of Iowa, 1975
M.S., Organic Chemistry, Indian Institute of Technology, 1971
B.S., Chemistry, Indian Institute of Technology, 1969
Research

News

Duquesne Compound To Fight Brain Cancer Earns Orphan Drug Status


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.

Courses

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

Honors/Awards

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 30 US patents; one European patent.

World Health Organization invited participant in collaborative research, 1998.

Granted the title of 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.

Received the President's Award for Faculty Excellence in Scholarship, Sept. 2014.

Grants, Contracts & Patents

Title: Small Molecule Microtubule Targeting Agents for Pancreatic Cancer
Agency: Commonwealth Universal research Enhancement (PA CURE)
Time: 06/01/2018 - 05/31/2022
Responsibility: Principal Investigator
Amount: $112,997

Title: Stabilizing the Cytoskeleton in Lewy Body Disease With Novel Bicyclic Microtubule Effectors
Agency: Samuel and Emma Winters Foundation
Time: 07/01/2019 - 06/30/2020
Responsibility: co-PI with Dr. Rehana Leak
Amount: $11,020.00

Title: Quelling Parkinson's Pathology with Novel Tricyclic Heterocycles that Stabilize the Microtubules of the Cellular Skeleton
Agency: Leach Foundation
Time: 07/01/2019 - 06/30/2021
Responsibility: co-PI with Dr. Rehana Leak
Amount: $25,000.00

Patents

Gangjee, A. US 9,556,198 B2. Tricyclic Compounds Having Antimitotic and/or Antitumor Activity and Methods of Use Thereof. Jan. 31, 2017.

Gangjee, A. US 9,624,178 B2. Substituted Cyclopenta Pyrimidine Bicyclic Compounds Having Antimitotic and/or Antitumor Activity Methods of Use Thereof. Apr. 18, 2017.

Gangjee, A. and Matherly, L. H. US 9,650,384 B2. Substituted Pyrimidine Compounds and Methods of Use and Manufacture. May 16, 2017.

Gangjee, A. US 9,688,690 B2. Pyrimidine Compounds and Pyrimido Indole Compounds and methods of Use. Jun. 27, 2017.

Gangjee, A. US 9,732,090 B2. Bicyclic and Tricyclic Pyrimidine Tryosine Kinase Inhibitors with Antitubulin Activity and Methods of Treating a Patient. Aug. 15, 2017.

Gangjee, A. US 9,777,012 B2. Substituted Furo[2,3-d]pyrimidines as Multi-Targeted Receptor Tyrosine Kinase Inhibitors and Microtubule Targeting Antitumor Agents. Oct. 3, 2017.

Gangjee, A. US 9,802,955 B2. Tricyclic Compounds Having Antimitotic and/or Antitumor activity and methods of Use Thereof. Oct. 31, 2017. Gangjee. A. US 9,896,455 B2. Tricyclic Compounds Having Cytostatic and/or Cytotoxic Activity and Methods of Use Thereof. Feb. 20, 2018.

Gangjee, A. US 9,987,283 B2. Tricyclic Compounds Having Antimitotic and/or Antitumor Activity and Methods of Use thereof. Jun. 5, 2018.

Gangjee, A. US 9,994,586 B2. Monocyclic, Thieno, Pyrido, and Pyrrolo Pyrimidine Compounds and Methods of Use and Manufacture of the Same. Jun. 12, 2018.

Gangjee, A. and Matherly, L. H. US 10,000,498 B2. Selective Proton Coupled Folate Transporter and Folate Receptor and GARFTase Inhibitor Compounds and Methods of Using the Same. Jun. 19, 2018.

Gangjee, A. US 10,072,019 B2. Substituted Pyrrolo, -Furano, and Cyclopentylpyrimidines Having Antimitotic and/or Antitumor Activity and Methods of Use Thereof. Sept. 11, 2018.

Gangjee, A. and Matherly, L. H. US 10,167,287 B2. Substituted Pyrimidine Compounds and Methods of Use and Manufacture. Jan. 1, 2019.

Gangjee, A. US 10,189,853 B2. Conformationally Restricted 4-Substituted 2,6-Dimethylfuro[2,3-d]pyrimidines as Anti-Tumor Agents. Jan. 29, 2019.

Gangjee, A. US 10,208,051 B2. Tricyclic Compounds Having Cytostatic and/or Cytotoxic Activity and Methods of Use Thereof. Feb. 19, 2019.

Gangjee, A. US 10,233,194 B2. Pyrimidine Compounds and Pyrimido Indole Compounds and Methods of Use. Mar. 19, 2019.

Gangjee, A. US 10,239,880 B2. Cyclopenta[d]pyrimidines and Substituted Cyclopenta[d]pyrimidines as Antitubulin and Microtubule Targeting Agents, Monocyclic Pyrimidines as Tubulin Inhibitors and Pyrrolopyrimidines as Targeted Antifolates and Tubulin and Multiple Receptor Tyrosine Kinase Inhibition and Antitumor Agents. Mar. 26, 2019.

Gangjee, A. US 10,358,450 B2. Substituted Bicyclic Pyrimidine Compounds with Tubulin and Multiple Receptor Inhibition. Jul. 23, 2019.

Gangjee, A. US 10,385,064 B2. Bicyclic and Tricyclic Pyrimidine Tyrosine Kinase Inhibitors with Antitubulin Activity and Methods of Treating a Patient. Aug. 20, 2019.

Gangjee, A. US 10,414,777 B2. Tricyclic Compounds Having Antimitotic and/or Antitumor Activity and Method of Use Thereof. Sept. 17, 2019.

Gangjee, A. US 10,457,688 B2. Monocyclic Thieno, Pyrido, and Pyrrolo Pyrimidine Compounds and Methods of Use and Manufacture of Same. Oct. 29, 2019.

Gangjee, A. US 10,464,944 B2. Tricyclic Compounds Having Antimitotic and/or Antitumor Activity and Methods of Use Thereof. Nov. 5, 2019.

Gangjee, A. US 10,538,527 B2. Cyclopenta[d]pyrimidines and Substituted Cyclopenta[d]-pyrimidines as Antitubulin and Microtubule Targeting Agents, Monocyclic Pyrimidines as Tubulin Inhibitors and Pyrrolopyrimidines as Targeted Antifolates and Tubulin and Multiple Receptor Tyrosine Kinase Inhibition and Antitumor Agents. Jan. 21, 2020.

Gangjee, A. US 10,577,377 B2. Substituted Cyclopenta Pyrimidine Bicyclic Compounds Having Antimitotic and/or Antitumor Activity and Methods of Use Thereof. Mar. 3, 2020.

Publications

Partial List

Ziegler, J.; Bastian, A.; Lerner, M.; Bailey-Downs, L.; Saunders, D.; Smith, N.; Sutton, J.; Battiste, J. D.; Ihnat, M. A.; Gangjee, A. and Towner, R. A. AG488 as a Therapy Against Gliomas. Oncotarget, on line publication May 30, 2017. https://doi.org/10.18632/oncotarget.18284

Devambatla, R. K. V.; Li, W.; Zaware, N.; Choudhary, S.; Hamel, E.; Mooberry, S. L. and Gangjee, A. Design, Synthesis, and Structure‒Activity Relationships of Pyrimido[4,5-b]indole-4-amines as Microtubule Depolymerizing Agents That Are Effective Against Multidrug Resistant Cells. Bioorg. Med. Chem. Letts., 2017, 27, 3423-3430. http://dx.doi.org/10.1016/j.bmcl.2017.05.085.

Ravindra, M.; Wallace-Povirk, A.; Karim, M. A.; Wilson, M. R.; O'Connor, C.; White, K.; Kushner, J.; Polin, L.; George, C.; Hou, Z.; Matherly, L. H. and Gangjee, A. Tumor Targeting with Novel Pyridyl 6-Substituted Pyrrolo[2,3-d]pyrimidine Antifolates via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of De Novo Purine Nucleotide Biosynthesis. J. Med. Chem., 2018, 61, 2027-2040. DOI: 10.1021/acs.jmdechem.7b01708. (Mar 2018)

Shah, K.; Raghavan, S.; Hou, Z.; Matherly, L. H. and Gangjee, A. Development and Validation of Chemical Features-Based Proton-Coupled Folate Transporter/Activity and Reduced Folate Carrier/Activity Models (Pharmacophores). J. Mol. Graph. Model. 2018, 81, 125-133. DOI: 10.1016/jmgm.s018.02.007. (May 2018)

Matherly, L. H.; Hou, Z. and Gangjee, A. The Promise and Challenges of Exploiting the Proton-Coupled Folate Transporter for Selective Therapeutic Targeting of Cancer. Cancer Chemother. Pharmacol., 2018, 81, 1-15. (Jan 2018)

Xiang, W.; Choudhary, S.; Hamel, E.; Mooberry, S. L. and Gangjee, A. Structure Based Drug Design and in vitro Metabolism Study: Discovery of N-(4-methylthiophenyl)-N,2-dimethyl-cyclopenta[d]pyrimidine as a Potent Microtubule Targeting Agent. Bioorg. Med. Chem., 2018, 26, 2437-2451. (May 2018) doi: https://doi.org/10.1016/j.bmc.2018.04.010. NIHMS 959865.

Ravindra, M.; Wilson, M.; Tong, N.; O'Connor, C.; Karim, M.; Polin, L.; Wallace-Povirk, A.; White, K.; Kushner, J.; Hou, Z,; Matherly, L. and Gangjee, A. Fluorine-Substituted Pyrrolo[2,3-d]pyrimidine Analogues with Tumor-Targeting via Cellular Uptake by Folate Receptor α and the Proton-Coupled Folate Transporter and Inhibition of de Novo Purine Nucleotide Biosynthesis. J. Med. Chem., 2018, 61, 4228-4248. doi: 10.1021/acs.jmedchem.8b00408. PMID: 29701475.

Shah, K.; Lin, X.; Queener, S. F.; Cody, V.; Pace, J. and Gangjee, A. Targeting Species Specific Amino Acid Residues: Design, Synthesis and Biological Evaluation of 6-Substituted Pyrrolo[2,3-d]pyrimidines as Dihydrofolate Reductase Inhibitors and Potential Anti-Opportunistic Infection Agents. Bioorg. Med. Chem., 2018, 26, 2640-2650. (May 2018). https://doi.org/10.1016/j.bmc.2018.04.032. NIHMS963403. Pub. ID. BMC14315.

Devambatla, R. K. V.; Choudhary, S.; Ihnat, M.; Hamel, E.; Mooberry, S. L. and Gangjee, A. Design, Synthesis and Preclinical Evaluation of 5-Methyl-N4-aryl-furo[2,3-d]pyrimidines as Single Agents with Combination Chemotherapy Potential. Bioorg. Med. Chem. Letts., 2018, 28, 3085-3093. doi: 10.1016/j.bmcl.2018.07.039. (Accepted July 2018).

Pavana, R. K.; Shah, K.; Gentile, T.; Dybdal-Hargreaves, N. F.; Risinger, A. L.; Mooberry, S. L.; Hamel, E. and Gangjee, A. Sterically Induced Conformational Retriction: Discovery and Preclinical Evaluation of Novel Pyrrolo[3,2-d]pyrimidines as Microtubule Targeting Agents. Bioorg. Med. Chem., 2018, 26, 5470-5478. https://doi.org.10.1016/j.bmc.2018.09.025. (Nov 2018)

Hou, Z.; O'Connor, C.; Frühauf, J.; Orr, S.; KIm, S.; Gangjee, A. and Matherly, L. H. Regulation of Differential Proton-Coupled Folate Transporter Gene Expression in Human Tumors: Transactivation by KLF15 with NRF-1 and the Role of Sp1. Biochem. J., 2019, 476, 1247-1266.
doi: 10.1042/BCJ20180394. (Apr 26, 2019).

Shah, K.; Queener, S.; Cody, V.; Pace, J. and Gangjee, A. Development of Substituted Pyrido[3,2-d]pyrimidines as Potent and Selective Dihydrofolate Reductase Inhibitors for Pneumocystis Pneumonia Infection. Bioorg. Med. Chem. Lett., 2019, 29, 1874-1880. (Jun 2019) https://doi.org/10.1016/j.bmcl.2019.06.004.

Dekhne, A. S.; Shah, K.; Ducker, G. S.; Katinas, J. M.; Wong-Roushar, J.; Nayeen, M. J.; Doshi, A.; Ning, C.; Bao, X.; Frühauf, J.; Liu, J.; Wallace-Povirk, A.; O'Connor, C.; Dzinic, S. H.; White, K.; Kushner, J.; Kim, S.; Hüttemann, M.; Polin, L.; Rabinowitz, J. D.; Li, J.; Hou, Z.; Dann, C. E.; Gangjee, A. and Matherly, L. H. Novel Pyrrolo[3,2-d]pyrimidine Compounds Target Mitochondrial and Cytosolic One-Carbon Metabolism with Broad-Spectrum antitumor Efficacy. Mol. Cancer Therap., 2019, 18, 1787-1799. Published on line 7/9/2019. DOI: 10.1158/1535-7163.MCT-19-0037.

Xiang, W.; Dekhne, A.; Doshi, A.; O'Connor, C.; Hou, Z.; Matherly, L. H. and Gangjee, A. Discovery of Amide-Bridged Pyrrolo[2,3-d]pyrimidines as Tumor Targeted Classical Antifolates with Selective Uptake by Folate Receptor α and Inhibition of de novo Purine Nucleotide Biosynthesis. Bioorg. Med. Chem., 2019, 27, 115-125. https://doi.org/10.1016/j.bmc.2019.115125.

Dekhne, A. S.; Ning, C.; Nayeen, M. J.; Shah, K.; Kalpage, H.; Frühauf, J.; Wallace-Povirk, A.; O'Connor, C.; Hou, Z.; Kim, S.; Hüttemann, M.; Gangjee, A. and Matherly, L. H. Cellular Pharmacodynamics of a Novel Pyrrolo-3,2-d]pyrimidine Inhibitor Targeting Mitochondrial and Cytosolic One-Carbon Metabolism. Mol. Pharmacol., 2020, 97, 9-22. https://doi.org/10.1124/mol.119.117937.

Golani, L. K.; Islam, F.; O'Connor, C.; Dehnke, A.; Hou, Z.; Matherly, L. H. and Gangjee, A. Design, Synthesis and Biological Evaluation of Novel Pyrrolo[2,3-d]pyrimidine as Tumor-Targeting Agents with Selectivity for Tumor Uptake by High Affinity Folate Receptors Over the Reduced Folate Carrier. Bioorg. Med. Chem. In press / May 2020.