Suneet  Shukla, Ph.D.
Suneet Shukla, Ph.D.
Staff Scientist

Center for Cancer Research
National Cancer Institute

Bldg. 37, Room 2120
Bethesda, MD 20892
301-435-6302

Development of modulators/inhibitors for ABC transporters In our efforts to screen and develop new inhibitors for the ABC transporters, we are exploring natural compounds for their inhibitory potential on ABC transporters. We have shown that curcumin isolated from turmeric powder, which is consumed daily as a spice in many countries and plumbagin, a napthoquinone from plant origin, inhibit the drug resistance mediated by drug transporters. We are also working on tyrosine kinase inhibitors for their inhibitory activity on ABC drug transporters. The newly developed tyrosine kinase inhibitor AMN107 (nilotinib) inhibits the tyrosine kinase activity of the BCR-ABL protein and is an effective, frontline therapy for chronic-phase CML. We have shown that it is a high affinity inhibitor of ABCG2 function.

Areas of Expertise
ABC transporters

Development of modulators/inhibitors for ABC transporters In our efforts to screen and develop new inhibitors for the ABC transporters, we are exploring natural compounds for their inhibitory potential on ABC transporters. We have shown that curcumin isolated from turmeric powder, which is consumed daily as a spice in many countries and plumbagin, a napthoquinone from plant origin, inhibit the drug resistance mediated by drug transporters. We are also working on tyrosine kinase inhibitors for their inhibitory activity on ABC drug transporters. The newly developed tyrosine kinase inhibitor AMN107 (nilotinib) inhibits the tyrosine kinase activity of the BCR-ABL protein and is an effective, frontline therapy for chronic-phase CML. We have shown that it is a high affinity inhibitor of ABCG2 function. We are characterizing its inhibitory activity on other ABC transporters now. We demonstrate that these inhibitors block ABCG2-mediated drug resistance and may increase oral bioavailability of ABCG2 substrates. Another area of focus for the development of inhibitors is the compounds from Developmental Therapeutics Program (DTP) chemical libraries. Based on structural similarity hits, several compounds from, DTP were projected to be potential inhibitors, our group is involved in a joint effort to screen the potential inhibitors of ABC transporters using these compounds

(This is an ongoing work in collaboration with Drs. Susan E Bates, Robert Robey, Heidi Bokesch, Kirk R Gustafson, Curtis Heinrich and Michael Dean, NCI, NIH).

Selected Publications
  1. Shukla S, Kouanda A, Silverton L, Talele TT, Ambudkar SV.
    Mol. Pharm.. 2014. [ Journal Article ]
  2. Bakhsheshian J, Wei BR, Chang KE, Shukla S, Ambudkar SV, Simpson RM, Gottesman MM, Hall MD.
    Proc. Natl. Acad. Sci. U.S.A.. 110: 20801-6, 2013. [ Journal Article ]
  3. Shukla S, Chufan EE, Singh S, Skoumbourdis AP, Kapoor K, Boxer MB, Duveau DY, Thomas CJ, Talele TT, Ambudkar SV.
    Leukemia. 28: 961-4, 2014. [ Journal Article ]
  4. Prasad B, Evers R, Gupta A, Hop CE, Salphati L, Shukla S, Ambudkar SV, Unadkat JD.
    Drug Metab. Dispos.. 42: 78-88, 2014. [ Journal Article ]
  5. Zhang H, Kathawala RJ, Wang YJ, Zhang YK, Patel A, Shukla S, Robey RW, Talele TT, Ashby CR, Ambudkar SV, Bates SE, Fu LW, Chen ZS.
    Int. J. Biochem. Cell Biol.. 51: 111-9, 2014. [ Journal Article ]

Dr Shukla obtained his Bachelor in Pharmacy (B. Pharmacy) from Hamdard University, New Delhi, India in 1996. He continued his interest in Pharmaceutical research and pursued Masters in Technology (M. Tech) from Jadavpur University, Calcutta, India in 1998 with a specialization in Biotechnology. He joined Jawaharlal Nehru University, New Delhi, India for his Ph.D degree where he worked on elucidating the mechanism of development of drug resistance in a pathogenic fungi, Candida albicans. He joined Laboratory of Cell Biology, NCI, NIH in 2004 as a postdoctoral fellow in Dr. Suresh V Ambudkar's group and continued his reserach on ABC drug transporters in multidrug resistant cancer cells. Currently, he is working as Staff Scientist in LCB, NCI, NIH.

Summary

Development of modulators/inhibitors for ABC transporters In our efforts to screen and develop new inhibitors for the ABC transporters, we are exploring natural compounds for their inhibitory potential on ABC transporters. We have shown that curcumin isolated from turmeric powder, which is consumed daily as a spice in many countries and plumbagin, a napthoquinone from plant origin, inhibit the drug resistance mediated by drug transporters. We are also working on tyrosine kinase inhibitors for their inhibitory activity on ABC drug transporters. The newly developed tyrosine kinase inhibitor AMN107 (nilotinib) inhibits the tyrosine kinase activity of the BCR-ABL protein and is an effective, frontline therapy for chronic-phase CML. We have shown that it is a high affinity inhibitor of ABCG2 function.

Areas of Expertise
ABC transporters

Research

Development of modulators/inhibitors for ABC transporters In our efforts to screen and develop new inhibitors for the ABC transporters, we are exploring natural compounds for their inhibitory potential on ABC transporters. We have shown that curcumin isolated from turmeric powder, which is consumed daily as a spice in many countries and plumbagin, a napthoquinone from plant origin, inhibit the drug resistance mediated by drug transporters. We are also working on tyrosine kinase inhibitors for their inhibitory activity on ABC drug transporters. The newly developed tyrosine kinase inhibitor AMN107 (nilotinib) inhibits the tyrosine kinase activity of the BCR-ABL protein and is an effective, frontline therapy for chronic-phase CML. We have shown that it is a high affinity inhibitor of ABCG2 function. We are characterizing its inhibitory activity on other ABC transporters now. We demonstrate that these inhibitors block ABCG2-mediated drug resistance and may increase oral bioavailability of ABCG2 substrates. Another area of focus for the development of inhibitors is the compounds from Developmental Therapeutics Program (DTP) chemical libraries. Based on structural similarity hits, several compounds from, DTP were projected to be potential inhibitors, our group is involved in a joint effort to screen the potential inhibitors of ABC transporters using these compounds

(This is an ongoing work in collaboration with Drs. Susan E Bates, Robert Robey, Heidi Bokesch, Kirk R Gustafson, Curtis Heinrich and Michael Dean, NCI, NIH).

Publications

Selected Publications
  1. Shukla S, Kouanda A, Silverton L, Talele TT, Ambudkar SV.
    Mol. Pharm.. 2014. [ Journal Article ]
  2. Bakhsheshian J, Wei BR, Chang KE, Shukla S, Ambudkar SV, Simpson RM, Gottesman MM, Hall MD.
    Proc. Natl. Acad. Sci. U.S.A.. 110: 20801-6, 2013. [ Journal Article ]
  3. Shukla S, Chufan EE, Singh S, Skoumbourdis AP, Kapoor K, Boxer MB, Duveau DY, Thomas CJ, Talele TT, Ambudkar SV.
    Leukemia. 28: 961-4, 2014. [ Journal Article ]
  4. Prasad B, Evers R, Gupta A, Hop CE, Salphati L, Shukla S, Ambudkar SV, Unadkat JD.
    Drug Metab. Dispos.. 42: 78-88, 2014. [ Journal Article ]
  5. Zhang H, Kathawala RJ, Wang YJ, Zhang YK, Patel A, Shukla S, Robey RW, Talele TT, Ashby CR, Ambudkar SV, Bates SE, Fu LW, Chen ZS.
    Int. J. Biochem. Cell Biol.. 51: 111-9, 2014. [ Journal Article ]

Biography

Dr Shukla obtained his Bachelor in Pharmacy (B. Pharmacy) from Hamdard University, New Delhi, India in 1996. He continued his interest in Pharmaceutical research and pursued Masters in Technology (M. Tech) from Jadavpur University, Calcutta, India in 1998 with a specialization in Biotechnology. He joined Jawaharlal Nehru University, New Delhi, India for his Ph.D degree where he worked on elucidating the mechanism of development of drug resistance in a pathogenic fungi, Candida albicans. He joined Laboratory of Cell Biology, NCI, NIH in 2004 as a postdoctoral fellow in Dr. Suresh V Ambudkar's group and continued his reserach on ABC drug transporters in multidrug resistant cancer cells. Currently, he is working as Staff Scientist in LCB, NCI, NIH.