IFITM proteins assist cellular uptake of diverse linked chemotypes-Reference-Cited by-同舟云学术

IFITM proteins assist cellular uptake of diverse linked chemotypes

Published:2022-12-09 Issue:6624 Volume:378 Page:1097-1104
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Lou Kevin¹²^ORCID,Wassarman Douglas R.¹²^ORCID,Yang Tangpo¹,Paung YiTing³^ORCID,Zhang Ziyang¹²⁴^ORCID,O’Loughlin Thomas A.⁵⁶^ORCID,Moore Megan K.¹²,Egan Regina K.⁷,Greninger Patricia⁷^ORCID,Benes Cyril H.⁷⁸,Seeliger Markus A.³^ORCID,Taunton Jack¹,Gilbert Luke A.⁵⁶⁹¹⁰^ORCID,Shokat Kevan M.¹²⁴^ORCID

Affiliation:

1. Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.

2. Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.

3. Department of Pharmacological Sciences, Stony Brook University, Stony Brook, NY 11794-8651, USA.

4. Department of Chemistry, University of California, Berkeley, Berkeley, CA 94720, USA.

5. Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94158, USA.

6. Department of Urology, University of California, San Francisco, San Francisco, CA 94158, USA.

7. Center for Cancer Research, Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA.

8. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.

9. Innovative Genomics Institute, University of California, San Francisco, San Francisco, CA 94158, USA.

10. Arc Institute, Palo Alto, CA 94304, USA.

Abstract

The search for cell-permeable drugs has conventionally focused on low-molecular weight (MW), nonpolar, rigid chemical structures. However, emerging therapeutic strategies break traditional drug design rules by employing flexibly linked chemical entities composed of more than one ligand. Using complementary genome-scale chemical-genetic approaches we identified an endogenous chemical uptake pathway involving interferon-induced transmembrane proteins (IFITMs) that modulates the cell permeability of a prototypical biopic inhibitor of MTOR (RapaLink-1, MW: 1784 g/mol). We devised additional linked inhibitors targeting BCR-ABL1 (DasatiLink-1, MW: 1518 g/mol) and EIF4A1 (BisRoc-1, MW: 1466 g/mol), uptake of which was facilitated by IFITMs. We also found that IFITMs moderately assisted some proteolysis-targeting chimeras and examined the physicochemical requirements for involvement of this uptake pathway.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Reference77 articles.

1. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

2. Molecular Properties That Influence the Oral Bioavailability of Drug Candidates

3. A Knowledge-Based Approach in Designing Combinatorial or Medicinal Chemistry Libraries for Drug Discovery. 1. A Qualitative and Quantitative Characterization of Known Drug Databases

4. Narcotic antagonistic potency of bivalent ligands which contain .beta.-naltrexamine. Evidence for simultaneous occupation of proximal recognition sites

5. Controlling Signal Transduction with Synthetic Ligands

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