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Current treatment options do not directly address this causal biology but focus on surgical and extra-sarcomeric (sarcolemmal) pharmacological symptomatic relief. Mavacamten (formerly known as MYK-461), is a small molecule designed to regulate cardiac function at the sarcomere level by selectively but reversibly inhibiting the enzymatic activity of myosin, the fundamental motor of the sarcomere. This review summarizes the mechanism and translational progress of mavacamten from proteins to patients, describing how the mechanism of action and pharmacological characteristics, involving both systolic and diastolic effects, can directly target pathophysiological derangements within the cardiac sarcomere to improve cardiac structure and function in HCM. Mavacamten was approved by the Food and Drug Administration in April 2022 for the treatment of obstructive HCM and now goes by the commercial name of Camzyos. Full information about the risks, limitations, and side effects can be found at\n            <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/214998s000lbl.pdf\">www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/214998s000lbl.pdf<\/jats:ext-link>\n            .\n          <\/jats:p>","DOI":"10.1126\/sciadv.abo7622","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T17:58:35Z","timestamp":1690567115000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":85,"title":["Mavacamten, a precision medicine for hypertrophic cardiomyopathy: From a motor protein to patients"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3355-2592","authenticated-orcid":true,"given":"Suman","family":"Nag","sequence":"first","affiliation":[{"name":"MyoKardia Inc., a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, CA 94005, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sampath K.","family":"Gollapudi","sequence":"additional","affiliation":[{"name":"MyoKardia Inc., a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, CA 94005, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9761-7888","authenticated-orcid":true,"given":"Carlos L.","family":"del Rio","sequence":"additional","affiliation":[{"name":"MyoKardia Inc., a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, CA 94005, USA."},{"name":"Cardiac Consulting, 1630 S Delaware St. #56426, San Mateo, CA 94403, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4324-4254","authenticated-orcid":true,"given":"James A.","family":"Spudich","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine, Stanford, CA 94305."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4029-5187","authenticated-orcid":true,"given":"Robert","family":"McDowell","sequence":"additional","affiliation":[{"name":"MyoKardia Inc., a wholly owned subsidiary of Bristol Myers Squibb, Brisbane, CA 94005, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.117.311059"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(65)90379-6"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.37.1.8"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318346"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12551-020-00721-5"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63703"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.2174\/1573403X1201160126125403"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11897-017-0346-8"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11886-020-01381-3"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.4330\/wjc.v2.i9.289"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11936-021-00934-1"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101297"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21249599"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22126617"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03971-y"},{"key":"e_1_3_1_17_2","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.20.3551"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.168583"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-019-02259-2"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA119.010563"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.1500511"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms8931"},{"key":"e_1_3_1_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-018-0069-x"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.49266"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140324"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212708110"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909468107"},{"key":"e_1_3_1_28_2","doi-asserted-by":"crossref","unstructured":"D. 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