Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

A Src SH2 selective binding compound inhibits osteoclast-mediated resorption.

S M Violette1, W C Shakespeare, C Bartlett

  • 1ARIAD Pharmaceuticals Inc., Biogen, Cambridge, Cambridge, MA 02139, USA. shelia_violette@biogen.com

Chemistry & Biology
|March 14, 2000
PubMed
Summary

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Estimating the impact of better management of glycaemic control in adults with Type 1 and Type 2 diabetes on the number of clinical complications and the associated financial benefit.

Diabetic medicine : a journal of the British Diabetic Association·2016
Same author

The role of candidate-gene CNTNAP2 in childhood apraxia of speech and specific language impairment.

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics·2015
Same author

The effects of two weeks of recombinant growth hormone administration on the response of IGF-I and N-terminal pro-peptide of collagen type III (P-III-NP) during a single bout of high resistance exercise in resistance trained young men.

Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society·2013
Same author

Comments on Waldeyer et al. 'Response to Hex et al. Estimating the current and future costs for Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs'.

Diabetic medicine : a journal of the British Diabetic Association·2013
Same author

Estimating the current and future costs of Type 1 and Type 2 diabetes in the UK, including direct health costs and indirect societal and productivity costs.

Diabetic medicine : a journal of the British Diabetic Association·2012
Same author

Successful use of Rusch balloon to control postpartum haemorrhage due to vaginal lacerations.

Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology·2011

A novel compound, AP22161, selectively inhibits the Src SH2 domain, effectively reducing osteoclast resorption. This discovery offers a promising therapeutic avenue for treating bone diseases like osteoporosis.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Pharmacology

Background:

  • Src tyrosine kinase is implicated in osteoclast-resorptive activity, evidenced by osteopetrosis in Src(-/-) mice.
  • Inhibitors of Src family tyrosine kinases reduce bone resorption mediated by osteoclasts.

Purpose of the Study:

  • To design and synthesize a selective Src SH2 domain inhibitor.
  • To evaluate the compound's efficacy in inhibiting Src-dependent cellular activity and osteoclast resorption.

Main Methods:

  • Designed AP22161 to target a cysteine residue in the Src SH2 phosphotyrosine-binding pocket.
  • Tested AP22161 in vitro for selective binding to the Src SH2 domain with high affinity.
  • Assessed AP22161 in cellular assays for its ability to block Src SH2 binding and inhibit osteoclast activity.

Related Experiment Videos

Main Results:

  • AP22161 demonstrated selective and high-affinity binding to the Src SH2 domain.
  • The compound effectively blocked Src SH2 binding to peptide ligands in cellular assays.
  • AP22161 significantly inhibited Src-dependent cellular activity and diminished osteoclast resorptive activity.

Conclusions:

  • A compound selectively inhibiting Src SH2 binding can effectively reduce osteoclast resorption.
  • AP22161 shows potential for development as a therapeutic agent for osteoporosis.