Science & Technology

Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology

Identification of potent pan-ephrin receptor kinase inhibitors using DNA-encoded chemistry technology

Technology tamfitronics

Significance

EPH receptors (EPHs) are extremely sought-after drug targets owing to their mandatory roles in affirming acceptable mobile functions in each and every physiological and disease circumstances. On the opposite hand, miniature potency and specificity pose most necessary boundaries to the event of tiny-molecule inhibitors for EPHs. Here, using excessive-throughput DNA-encoded chemical library screenings, we developed potent and selective inhibitors of the EPH receptor kinase family. Our outcomes moreover emphasize the therapeutic attainable of our EPH inhibitors in cancer and endometriosis, a global health wretchedness that causes chronic pain and veritably ends in infertility in ladies. This secret agent showcases the tough pipeline of using DNA-encoded chemistry technology to title nonhormonal therapeutic agents tailored for the treatment of gynecologic diseases, including, but no longer miniature to, endometriosis.

Summary

EPH receptors (EPHs), the finest family of tyrosine kinases, phosphorylate downstream substrates upon binding of ephrin cell surface–associated ligands. In a spruce cohort of endometriotic lesions from folks with endometriosis, we stumbled on that EPHA2 and EPHA4 expressions are increased in endometriotic lesions relative to typical eutopic endometrium. Because signaling through EPHs is associated with increased cell migration and invasion, we hypothesized that chemical inhibition of EPHA2/4 may perhaps likely have therapeutic mark. We screened DNA-encoded chemical libraries (DECL) to impulsively title EPHA2/4 kinase inhibitors. Hit compound, CDD-2693, exhibited picomolar/nanomolar kinase exercise towards EPHA2 (Ki: 4.0 nM) and EPHA4 (Ki: 0.81 nM). Kinome profiling revealed that CDD-2693 sure to most EPH family and SRC family kinases. Using NanoBRET goal engagement assays, CDD-2693 had nanomolar exercise versus EPHA2 (IC50: 461 nM) and EPHA4 (IC50: 40 nM) but changed into a micromolar inhibitor of SRC, YES, and FGR. Chemical optimization produced CDD-3167, having picomolar biochemical exercise toward EPHA2 (Ki: 0.13 nM) and EPHA4 (Ki: 0.38 nM) with gorgeous cell-essentially essentially essentially based potency EPHA2 (IC50: 8.0 nM) and EPHA4 (IC50: 2.3 nM). Moreover, CDD-3167 maintained superior off-goal mobile selectivity. In 12Z endometriotic epithelial cells, CDD-2693 and CDD-3167 very a lot lowered EFNA5 (ligand) induced phosphorylation of EPHA2/4, lowered 12Z cell viability, and lowered IL-1β-mediated expression of prostaglandin synthase 2 (PTGS2). CDD-2693 and CDD-3167 lowered growth of valuable endometrial epithelial organoids from patients with endometriosis and lowered Ewing’s sarcoma viability. Thus, using DECL, we identified potent pan-EPH inhibitors that prove specificity and exercise in mobile units of endometriosis and cancer.

Get plump earn entry to to this article

Acquire, subscribe or point out this article to your librarian.

Technology tamfitronics Files, Materials, and Tool Availability

All secret agent data are integrated within the article and/or SI Appendix.

Technology tamfitronics Acknowledgments

We thank Xuan Qin and Jian Wang for his or her assistance in producing the metabolic steadiness and Excessive Resolution Mass Spectrometry data for this secret agent. This examine is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Constructing [grants R33HD099995 (F.L.), R01HD105800, HD096057 (D.M.), and R01HD110038 (M.M.M.)]. D.M. is supported by a Next Gen Pregnancy Award from the Burroughs Welcome Fund (NGP10125). C.J.C. is supported by the Dan L. Duncan Cancer Center Grant CA125123. M.P. is supported by NIH grant R03CA259664 and a grant from the Cancer Prevention Analysis Institute of Texas (CPRIT), RP220524. Z.T. is a CPRIT pupil in cancer examine and thanks CPRIT for examine funding toughen (RR220039).

Author contributions

C.M., Z.L., S.E.P., K.L.S., K.M.B., Q.Y., F.L., M.P., Z.T., F.Y., C.J.C., S.T., R.P.M., D.W.Y., D.M., and M.M.M. designed examine; C.M., Z.L., S.E.P., K.L.S., K.M.B., F.L., M.P., Z.T., F.Y., C.J.C., S.T., and D.M. performed examine; C.M. and X.G. contributed original reagents/analytic tools; C.M., Z.L., S.E.P., K.L.S., K.M.B., Q.Y., F.L., M.P., Z.T., F.Y., C.J.C., S.T., R.P.M., D.W.Y., and D.M. analyzed data; and C.M., Z.L., S.E.P., K.L.S., K.M.B., Q.Y., F.L., M.P., Z.T., F.Y., S.T., D.W.Y., D.M., and M.M.M. wrote the paper.

Competing interests

The authors repeat no competing passion.

Technology tamfitronics Supporting Files

Technology tamfitronics References

1

A. Poliakov, M. Cotrina, D. G. Wilkinson, Diverse roles of eph receptors and ephrins within the regulation of cell migration and tissue assembly. Dev. Cell 7465–480 (2004).

2

T. K. Niethamer, J. O. Bush, Getting direction(s): The Eph/ephrin signaling machine in cell positioning. Dev. Biol. 44742–57 (2019).

3

K. K. Murai, E. B. Pasquale, ’Eph’ective signaling: Forward, reverse and crosstalk. J. Cell Sci. 1162823–2832 (2003).

4

T. K. Darling, T. J. Lamb, Emerging roles for Eph receptors and ephrin ligands in immunity. Entrance. Immunol. 101473 (2019).

5

J. Egea, R. Klein, Bidirectional Eph-ephrin signaling throughout axon steering. Traits Cell Biol. 17230–238 (2007).

6

K. O. Lai, N. Y. Ip, Synapse sort and plasticity: Roles of ephrin/Eph receptor signaling. Curr. Opin. Neurobiol. 19275–283 (2009).

7

K. Ellis, D. Munro, J. Clarke, Endometriosis is undervalued: A call to action. Entrance. Glob. Womens Health 3902371 (2022).

8

L. Saavalainen et al., Be troubled of gynecologic cancer in accordance to the form of endometriosis. Obstet. Gynecol. 1311095–1102 (2018).

9

P. Vercellini, P. Vigano, E. Somigliana, L. Fedele, Endometriosis: Pathogenesis and treatment. Nat. Rev. Endocrinol. 10261–275 (2014).

10

C. To et al., Hypoxia-controlled EphA3 marks a human endometrium-derived multipotent mesenchymal stromal cell that helps vascular development. PLoS One 9e112106 (2014).

11

H. Fujiwara et al., Promoting roles of embryonic indicators in embryo implantation and placentation in cooperation with endocrine and immune techniques. Int. J. Mol. Sci. 211885 (2020).

12

Y. Fu, J. Fu, Q. Ren, X. Chen, A. Wang, Expression of Eph A molecules throughout swine embryo implantation. Mol. Biol. Safe. 392179–2185 (2012).

13

Y. Fu et al., Investigation of Eph-ephrin A1 within the regulation of embryo implantation in sows. Reprod. Domest. Anim. Fifty three1563–1574 (2018).

14

H. Fujii et al., Eph-ephrin A machine regulates murine blastocyst attachment and spreading. Dev. Man. 2353250–3258 (2006).

15

A. A. Kamat et al., EphA2 overexpression is associated with lack of hormone receptor expression and unfortunate in endometrial cancer. Cancer 1152684–2692 (2009).

16

L. D. Dong et al., Overexpression of erythropoietin-producing hepatocyte receptor B4 and ephrin-B2 is associated with estrogen receptor expression in endometrial adenocarcinoma. Oncol. Lett. 132109–2114 (2017).

17

I. Psilopatis, A. Pergaris, K. Vrettou, G. Tsourouflis, S. Theocharis, The EPH/Ephrin machine in gynecological cancers: Focusing on the roots of carcinogenesis for better patient administration. Int. J. Mol. Sci. 233249 (2022).

18

A. V. Buensuceso et al., Ephrin-A5 is required for optimal fertility and a entire ovulatory response to gonadotropins within the female mouse. Endocrinology 157942–955 (2016).

19

R. Hudecek, B. Kohlova, I. Siskova, M. Piskacek, A. Knight, Blockading of EphA2 on endometrial tumor cells reduces susceptibility to Vdelta1 gamma-delta T-cell-mediated killing. Entrance. Immunol. 12752646 (2021).

20

E. A. Adu-Gyamfi et al., Ephrin and Eph receptor signaling in feminine reproductive physiology and pathologydagger. Biol. Reprod. 10471–82 (2021).

21

E. B. Pasquale, Eph receptors and ephrins in cancer: Bidirectional signalling and beyond. Nat. Rev. Cancer 10165–180 (2010).

22

N. J. Balamuth, R. B. Womer, Ewing’s sarcoma. Lancet Oncol. 11184–192 (2010).

23

M. Sainz-Jaspeado et al., EphA2-induced angiogenesis in ewing sarcoma cells works through bFGF manufacturing and depends on caveolin-1. PLoS One 8e71449 (2013).

24

G. Giordano et al., EphA2 expression in bone sarcomas: Bioinformatic analyses and preclinical characterization in patient-derived units of osteosarcoma, Ewing’s sarcoma and chondrosarcoma. Cells 102893 (2021).

25

N. Cheng et al., Inhibition of VEGF-dependent multistage carcinogenesis by soluble EphA receptors. Neoplasia 5445–456 (2003).

26

P. Dobrzanski et al., Antiangiogenic and antitumor efficacy of EphA2 receptor antagonist. Cancer Res. 64910–919 (2004).

27

N. Cheng et al., Blockade of EphA receptor tyrosine kinase activation inhibits vascular endothelial cell development part-induced angiogenesis. Mol. Cancer Res. 12–11 (2002).

28

L. W. Noblitt et al., Decreased tumorigenic attainable of EphA2-overexpressing breast cancer cells following treatment with adenoviral vectors that categorical EphrinA1. Cancer Gene Ther. 11757–766 (2004).

29

Noren NK, Lu M, Freeman AL, Koolpe M, Pas EB quale, Interplay between EphB4 on tumor cells and vascular ephrin-B2 regulates tumor development. Proc. Natl. Acad. Sci. U.S.A. 1015583–5588 (2004).

30

M. Koolpe, M. Dail, E. B. Pasquale, An ephrin mimetic peptide that selectively targets the EphA2 receptor. J. Biol. Chem. 27746974–46979 (2002).

31

M. W. Karaman et al., A quantitative diagnosis of kinase inhibitor selectivity. Nat. Biotechnol. 26127–132 (2008).

32

L. Qiao et al., Construction-exercise relationship secret agent of EphB3 receptor tyrosine kinase inhibitors. Bioorg Med. Chem. Easy. 196122–6126 (2009).

33

Y. Choi et al., Discovery and structural diagnosis of Eph receptor tyrosine kinase inhibitors. Bioorg Med. Chem. Easy. 194467–4470 (2009).

34

RM Franzini, D. Neri, J. Scheuermann, DNA-encoded chemical libraries: Advancing beyond historical small-molecule libraries. Acc Chem. Res. 471247–1255 (2014).

35

Y. K. Sunkari, V. K. Siripuram, T. L. Nguyen, M. Flajolet, Excessive-strength screening (HPS) empowered by DNA-encoded libraries. Traits Pharmacol. Sci. 434–15 (2022).

36

AL Satz et al., DNA-encoded chemical libraries. Nat. Rev. Ideas Primers 23 (2022).

37

A. Gironda-Martinez, E. J. Donckele, F. Samain, D. Neri, DNA-encoded chemical libraries: A entire assessment with succesful tales and future challenges. ACS Pharmacol. Transl. Sci. 41265–1279 (2021).

38

J. C. Faver et al., Quantitative comparability of enrichment from DNA-encoded chemical library picks. ACS Comb. Sci. 2175–82 (2019).

39

J. Zhang, L. Wang, Q. Ji, F. Liu, DNA-Suitable cyanomethylation of (hetero)aryl halides or triflates under a tandem reaction for DNA-encoded library synthesis. Org. Lett. 256931–6936 (2023).

40

Z. Yu et al., Discovery and characterization of bromodomain 2-dispute inhibitors of BRDT. Proc. Natl. Acad. Sci. U.S.A. 118e2021102118 (2021).

41

R. K. Modukuri et al., Discovery of potent BET bromodomain 1 stereoselective inhibitors using DNA-encoded chemical library picks. Proc. Natl. Acad. Sci. U.S.A. 119e2122506119 (2022).

42

R. K. Modukuri et al., Discovery of extremely potent and BMPR2-selective kinase inhibitors using DNA-encoded chemical library screening. J. Med. Chem. 662143–2160 (2023).

43

R. Jimmidi et al., DNA-encoded chemical libraries yield non-covalent and non-peptidic SARS-CoV-2 valuable protease inhibitors. Commun. Chem. 6164 (2023).

44

M. Gabriel et al., A relational database to title differentially expressed genes within the endometrium and endometriosis lesions. Sci. Files 7284 (2020).

45

J. S. Tamaresis et al., Molecular classification of endometriosis and disease stage using excessive-dimensional genomic data. Endocrinology 1554986–4999 (2014).

46

M. I. Kurki et al., FinnGen provides genetic insights from a effectively-phenotyped isolated population. Nature 613508–518 (2023).

47

M. A. Fabian et al., A tiny molecule-kinase interaction blueprint for medical kinase inhibitors. Nat. Biotechnol. 23329–336 (2005).

Forty eight

A. Zeitvogel, R. Baumann, A. Starzinski-Powitz, Identification of an invasive, N-cadherin-expressing epithelial cell kind in endometriosis using a brand original cell tradition model. Am. J. Pathol. 1591839–1852 (2001).

49

J. Arnold et al., Imbalance between sympathetic and sensory innervation in peritoneal endometriosis. Mind Behav. Immun. 26132–141 (2012).

50

V. Anaf et al., Relationship between endometriotic foci and nerves in rectovaginal endometriotic nodules. Hum. Reprod. 151744–1750 (2000).

51

B. D. McKinnon, D. Bertschi, N. A. Bersinger, M. D. Mueller, Inflammation and nerve fiber interaction in endometriotic pain. Traits Endocrinol. Metab 261–10 (2015).

52

Induction of COX-2 and PGE(2) biosynthesis by IL-1beta is mediated by PKC and mitogen-activated protein kinases in murine astrocytes. Br. J. Pharmacol. 131152–159 (2000).

Fifty three

T. Takahashi, Organoids for drug discovery and personalized medication. Annu. Rev. Pharmacol. Toxicol. 59447–462 (2019).

54

M. Y. Turco et al., Long-interval of time, hormone-responsive organoid cultures of human endometrium in a chemically defined medium. Nat. Cell Biol. 19568–577 (2017).

55

Y. Hibaoui, A. Feki, Organoid units of human endometrial sort and disease. Entrance Cell Dev. Biol. 884 (2020).

56

M. Boretto et al., Constructing of organoids from mouse and human endometrium exhibiting endometrial epithelium physiology and long-interval of time expandability. Constructing 1441775–1786 (2017).

57

N. I. Herath et al., Over-expression of Eph and ephrin genes in stepped forward ovarian cancer: Ephrin gene expression correlates with shortened survival. BMC Cancer 6144 (2006).

58

L. Han et al., The medical significance of EphA2 and Ephrin A-1 in epithelial ovarian carcinomas. Gynecol. Oncol. Ninety 9278–286 (2005).

59

X. Liu et al., EphA8 is a prognostic marker for epithelial ovarian cancer. Oncotarget 720801–20809 (2016).

60

G. Berclaz et al., Activation of the receptor protein tyrosine kinase EphB4 in endometrial hyperplasia and endometrial carcinoma. Ann. Oncol. 14220–226 (2003).

61

S. M. Alam, J. Fujimoto, I. Jahan, E. Sato, T. Tamaya, Overexpression of ephrinB2 and EphB4 in tumor sort of uterine endometrial cancers. Ann. Oncol. 18485–490 (2007).

62

W. M. Merritt et al., Clinical and biological affect of EphA2 overexpression and angiogenesis in endometrial cancer. Cancer Biol. Ther 101306–1314 (2010).

63

S. Reinartz et al., A transcriptome-essentially essentially essentially based global blueprint of signaling pathways within the ovarian cancer microenvironment associated with medical . Genome Biol. 17108 (2016).

64

P. H. Thaker et al., EphA2 expression is associated with aggressive functions in ovarian carcinoma. Clin. Cancer Res. 105145–5150 (2004).

65

H. Fujii, H. Fujiwara, A. Horie, Y. Sato, I. Konishi, Ephrin A1 induces intercellular dissociation in Ishikawa cells: Most likely implication of the Eph-ephrin A machine in human embryo implantation. Hum. Reprod. 26299–306 (2011).

66

Y. Yang, J. Min, Attain of ephrin-A1/EphA2 on invasion of trophoblastic cells. J. Huazhong Univ. Sci. Technol. Med. Sci. 31824–827 (2011).

67

H. Fujiwara et al., Eph-ephrin A machine regulates human choriocarcinoma-derived JEG-3 cell invasion. Int. J. Gynecol. Cancer 23576–582 (2013).

68

X. Y. Yang, W. J. Zhu, H. Jiang, Activation of erythropoietin-producing hepatocellular receptor A2 attenuates cell adhesion of human fallopian tube epithelial cells by project of focal adhesion kinase dephosphorylation. Mol. Cell Biochem. 361259–265 (2012).

69

H. Jiang, X. Y. Yang, W. J. Zhu, Dysregulated erythropoietin-producing hepatocellular receptor A2 (EphA2) is thinking tubal being pregnant by project of regulating cell adhesion of the Fallopian tube epithelial cells. Reprod. Biol. Endocrinol. 1684 (2018).

70

Y. Zhang et al., Elevated ranges of hypoxia-inducible microRNA-210 in pre-eclampsia: Novel insights into molecular mechanisms for the disease. J. Cell Mol. With. 16249–259 (2012).

71

W. Wang et al., Preeclampsia up-regulates angiogenesis-associated microRNA (i.e., miR-17, -20a, and -20b) that specialise in ephrin-B2 and EPHB4 in human placenta. J. Clin. Endocrinol. Metab. 97E1051–1059 (2012).

72

N. Ilan, J. A. Madri, Novel paradigms of signaling within the vasculature: Ephrins and metalloproteases. Curr. Opin. Biotechnol. 10536–540 (1999).

73

L. Schrödinger, Schrödinger Release 2022–1 (Schrödinger LLC, Novel York, NY, 2022).

74

L. Schrödinger, Schrödinger Release 2022–1: LigPrep (Schrödinger, LLC, Novel York, NY, 2022).

75

R. C. Johnston et al., Epik: pK(a) and protonation affirm prediction through machine discovering out. J. Chem. Thought Comput. 192380–2388 (2023).

76

R. A. Friesner et al., Extra precision slip with the movement: Docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes. J. Med. Chem. 496177–6196 (2006).

77

L. Schrödinger, Schrödinger Release 2023–4: Maestro (Schrödinger, LLC, Novel York, NY, 2022).

78

T. Yang et al., Therapeutic HNF4A mRNA attenuates liver fibrosis in a preclinical model. J. Hepatol. 751420–1433 (2021).

Seventy 9

C. A. Schneider, W. S. Rasband, K. W. Eliceiri, NIH Image to ImageJ: 25 years of image diagnosis. Nat. Ideas 9671–675 (2012).

80

H. C. Fitzgerald, P. Dhakal, S. K. Behura, D. J. Schust, T. E. Spencer, Self-renewing endometrial epithelial organoids of the human uterus. Proc. Natl. Acad. Sci. U.S.A. 11623132–23142 (2019).

Technology tamfitronics Files & Authors

Files

Printed in

Technology tamfitronics Hump to Complaints of the National Academy of Sciences

Complaints of the National Academy of Sciences

Vol. 121 | No. 19
May likely perhaps 7, 2024

Classifications

Copyright

Files, Materials, and Tool Availability

All secret agent data are integrated within the article and/or SI Appendix.

Submission history

Got: December 28, 2023

Well-liked: March 22, 2024

Printed online: May likely perhaps 3, 2024

Printed in mutter: May likely perhaps 7, 2024

Keywords

  1. DNA-encoded chemistry
  2. ephrin receptor kinase inhibitors
  3. endometriosis

Acknowledgments

We thank Xuan Qin and Jian Wang for his or her a ssistance in producing the metabolic steadiness and Excessive Resolution Mass Spectrometry data for this secret agent. This examine is supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Constructing [grants R33HD099995 (F.L.), R01HD105800, HD096057 (D.M.), and R01HD110038 (M.M.M.)]. D.M. is supported by a Next Gen Pregnancy Award from the Burroughs Welcome Fund (NGP10125). C.J.C. is supported by the Dan L. Duncan Cancer Center Grant CA125123. M.P. is supported by NIH grant R03CA259664 and a grant from the Cancer Prevention Analysis Institute of Texas (CPRIT), RP220524. Z.T. is a CPRIT pupil in cancer examine and thanks CPRIT for examine funding toughen (RR220039).

Author Contributions

C.M., Z.L., S.E.P., K.L.S., K.M.B., Q.Y., F.L., M.P., Z.T., F.Y., C.J.C., S.T., R.P.M., D.W.Y., D.M., and M.M.M. designed examine; C.M., Z.L., S.E.P., K.L.S., K.M.B., F.L., M.P., Z.T., F.Y., C.J.C., S.T., and D.M. performed examine; C.M. and X.G. contributed original reagents/analytic tools; C.M., Z.L., S.E.P., K.L.S., K.M.B., Q.Y., F.L., M.P., Z.T., F.Y., C.J.C., S.T., R.P.M., D.W.Y., and D.M. analyzed data; and C.M., Z.L., S.E.P., K.L.S., K.M.B., Q.Y., F.L., M.P., Z.T., F.Y., S.T., D.W.Y., D.M., and M.M.M. wrote the paper.

Competing Pursuits

The authors repeat no competing passion.

Notes

Reviewers: T.D.C., Sanford Burnham Prebys Scientific Discovery Institute; and Y.W., Alive to Therapeutics.

Authors

Affiliations

Chandrashekhar Madasu1

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Molecular and Human Genetics, Baylor College of Tablets, Houston, TX 77030

Sydney E. Parks

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Biochemistry and Molecular Pharmacology, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Zhi Tan

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Biochemistry and Molecular Pharmacology, Baylor College of Tablets, Houston, TX 77030

Fei Yuan

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Chad J. Creighton

Dan L. Duncan Whole Cancer Center Division of Biostatistics, Baylor College of Tablets, Houston, TX 77030

Human Genome Sequencing Center, Baylor College of Tablets, Houston, TX 77030

Department of Tablets, Baylor College of Tablets, Houston, TX 77030

A dog Tang

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Ramya P. massaging

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Department of Obstetrics and Gynecology, Baylor College of Tablets, Houston, TX 77030

Xiaoming Guan

Department of Obstetrics and Gynecology, Baylor College of Tablets, Houston, TX 77030

Damian W. Younger

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Biochemistry and Molecular Pharmacology, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Pathology and Immunology, Baylor College of Tablets, Houston, TX 77030

Center for Drug Discovery, Baylor College of Tablets, Houston, TX 77030

Department of Molecular and Human Genetics, Baylor College of Tablets, Houston, TX 77030

Department of Biochemistry and Molecular Pharmacology, Baylor College of Tablets, Houston, TX 77030

Notes

1

C.M. and Z.L. contributed equally to this work.

Technology tamfitronics Metrics & Citations

Metrics

Show veil: The article usage is offered with a three- to four-day delay and can change every day once accessible. As a consequence of ths delay, usage data is no longer going to examine once following e-newsletter. Citation data is sourced from Crossref Cited-by provider.

Citation statements

Altmetrics

Citations

In the event you’ve got the correct tool installed, you may perhaps perhaps likely download article quotation data to the quotation manager of your different. Simply pick your manager tool from the checklist below and click on Download.

Technology tamfitronics Peep Alternate choices

Get Get precise of entry to

Peep alternate choices

PDF layout

Download this article as a PDF file

DOWNLOAD PDF

Technology tamfitronics Media

Figures

Tables

Varied

Spread the love

Leave a Reply