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The annual "star" small molecule list is released, including long-acting HIV therapy, PROTAC molecules, KRAS inhibitors...

 Last Update: 2021-04-19
 Source: Internet
 Author: User

▲The annual list of small molecule drugs published on the Lieyaoren website (picture source: reference [1] )

▲Annual list of small molecule drugs published on the Lieyaoren website (picture source: reference [1] ) ▲Annual list of small molecule drugs published on the Lieyaoren website (picture source: reference [1] ) )544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>The top-ranked lenacapavir is one of the key drugs in the weixin.
qq.
com/s?__biz=MzAwMDA5NTIxNQ==&mid=2650003765&idx=2&sn=082819103e8058cf4d4d56cc6c4aa4d6&scene=21#wechat_redirect" textvalue="" tab="innerlink" data-linktype="2" style="margin:0px;padding:0px;color:#576B95;text-decoration-line:none;-webkit-tap-highlight-color:rgba(0, 0, 0, 0);cursor:pointer;max-width:100%;box-sizing:border-box ;overflow-wrap:break-word ;">recent major research and development cooperation between Gilead Sciences and Merck & Co.
( MSD ) in the HIV field .

▲ Basic structure of HIV virus (picture source: reference [4] )

▲ Basic structure of the HIV virus (picture source: reference [4] ) ▲ Basic structure of the HIV virus (picture source: reference [4] ) basic structure of the virus (picture source: reference )544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>This capsid is formed by the self-assembly of thousands of capsid protein monomers.
Capsid protein monomers are a bit like Lego building blocks.
Each small building block can be put together to form a pentamer or hexamer, and then these pentamers and hexamers are joined together to form a complete capsid.
Due to the importance of capsids in the HIV replication process, drug development targeting capsids has long been the direction of research and development personnel to explore.
Gilead Sciences began research in this area in 2006 .

▲The HIV capsid is like a model made up of many small building blocks (capsid protein monomers) (picture source: reference [5] )

▲The HIV capsid is like a model made up of many small building blocks (capsid protein monomers) (picture source: reference [5] ) ▲The HIV capsid is like a model made up of many small building blocks (capsid protein monomers) The assembled model (picture source: reference [5] ) The capsid is like a model made up of many small building blocks (capsid protein monomer) (picture source: reference [5] )544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>Lenacapavir : Make HIV capsid a "fake and shoddy product"Lenacapavir : Let the HIV capsid become a "fake and shoddy product" Lenacapavir : Let the HIV capsid become a "fake and shoddy product" : Let the capsid become a "fake and shoddy product"544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>Just as a good Lego model requires every small building block to be stitched together tightly, the normal function of the capsid also requires the precise assembly of the capsid protein monomers.
So, if it can affect the self-assembly process of the capsid protein monomer, can it disrupt the function of the capsid and the replication process of HIV ?Just as a good Lego model requires every small building block to be stitched together tightly, the normal function of the capsid also requires the precise assembly of the capsid protein monomers.
So, if it can affect the self-assembly process of the capsid protein monomer, can it disrupt the function of the capsid and the replication process of HIV ? Just as a good Lego model requires every small building block to be stitched together tightly, the normal function of the capsid also requires the precise assembly of the capsid protein monomers.
So, if it can affect the self-assembly process of the capsid protein monomer, can it disrupt the function and replication process of the capsid ?544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>This is also the direction of the development of drug discovery and development personnel, in 2010 year Pfizer ( Pfizer ) the company's R & D personnel in PLOS Pathogens study published in, showing the crystal structure of the company to develop inhibitors of the capsid protein capsid monomer combination The model, although the potency of this candidate compound is not high, it proves the feasibility of targeting the capsid.
This is also the direction of the development of drug discovery and development personnel, in 2010 year Pfizer ( Pfizer ) the company's R & D personnel in PLOS Pathogens study published in, showing the crystal structure of the company to develop inhibitors of the capsid protein capsid monomer combination The model, although the potency of this candidate compound is not high, it proves the feasibility of targeting the capsid.
This is also the direction of drug R&D personnel.
In a study published on PLOS Pathogens by Pfizer ( ) R&D personnel , they demonstrated the crystal structure model of the capsid inhibitor combined with the capsid protein monomer developed by the company.
Although the potency of this candidate compound is not high, it proves the feasibility of targeting the capsid.
544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>Based on this idea, the R&D team of Gilead Sciences screened drugs that affect the capsid assembly process.
They found that it is difficult to find inhibitors that inhibit capsid assembly.
This may be because the concentration of the capsid protein monomer in the virus is too high for the inhibitor to work.
However, the candidate compounds that accelerate the assembly of the capsid produced better results.
By combining with the capsid protein monomer , lenacapavir not only speeds up the assembly of the viral capsid, but also makes the resulting capsid a dysfunctional "fake product.

▲Lenacapavir ( GS-6207 ) has significantly improved activity compared with the original capsid inhibitor (picture source: reference [1] )

▲Lenacapavir ( GS-6207 ) has significantly improved activity compared with the original capsid inhibitor (picture source: Reference [1] ) ▲Lenacapavir ( GS-6207 ) has significantly increased activity compared with the original capsid inhibitor (Image source: Reference [1] ) ( GS-6207 ) Compared with the original capsid inhibitor, the activity is significantly improved (Image source: Reference [1] )

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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>Brings hope for long-acting HIV therapyBringing hope to long -acting HIV therapy Bringing hope to long-acting HIV therapy Bringing hope to long-actingtherapy544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>Another difficulty in developing long-acting HIV therapy is to prevent the drug from being cleared by the liver.
The modification of lenacapavir by the Gilead scientific team gives it a long half-life, so that it may only need to receive treatment every 6 months to maintain the antiviral effect.
.
In 2019 Nian 5 months, it has received FDA breakthrough therapy identified granted, and in combination with other antiviral drugs, the treatment of drug resistance to multiple drugs HIV -infected persons.
At a medical conference held this month, lenacapavir achieved positive results in the Phase 2/3 clinical trial CAPELLA for the treatment of HIV- infected individuals who are resistant to multiple antiviral drugs .
Combined with an optimized background treatment plan, receiving a subcutaneous injection of lenacapavir allows 73% of patients to maintain their HIV virus levels at undetectable levels after 26 weeks of treatment .
Gilead Sciences expects to submit a regulatory application to the US FDA in the second half of this year .
Another difficulty in developing long-acting HIV therapy is to prevent the drug from being cleared by the liver.
The modification of lenacapavir by the Gilead scientific team gives it a long half-life, so that it may only need to receive treatment every 6 months to maintain the antiviral effect.
.
In 2019 Nian 5 months, it has received FDA breakthrough therapy identified granted, and in combination with other antiviral drugs, the treatment of drug resistance to multiple drugs HIV -infected persons.
At a medical conference held this month, lenacapavir achieved positive results in the Phase 2/3 clinical trial CAPELLA for the treatment of HIV- infected individuals who are resistant to multiple antiviral drugs .
Combined with an optimized background treatment plan, receiving a subcutaneous injection of lenacapavir allows 73% of patients to maintain their HIV virus levels at undetectable levels after 26 weeks of treatment .

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75em;text-align:center;box-sizing:border-box ;overflow-wrap:break-word ;'>Image source: Gilead Sciences' official websiteImage source: Gilead Sciences' official website544px;text-align:justify;white-space:normal;background-color:#FFFFFF;line-height:1.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>In addition to being a long-acting therapy for HIV- infected patients, Gilead Sciences is also conducting clinical trials to evaluate the potential of lenacapavir as a pre-exposure prophylaxis ( PrEP ) therapy.
In preclinical non-human primate studies, a low-dose or high-dose lenacapavir injection can reduce the risk of infection by 86% ( p=0.
0061 ) and 96% ( p=0.
0002 ), respectively.
In addition to being a long-acting therapy for HIV- infected patients, Gilead Sciences is also conducting clinical trials to evaluate the potential of lenacapavir as a pre-exposure prophylaxis ( PrEP ) therapy.
In preclinical non-human primate studies, a low-dose or high-dose lenacapavir injection can reduce the risk of infection by 86% ( p=0.
0061 ) and 96% ( p=0.
0002 ), respectively.
In addition to being a long-acting therapy for the treatment of infected people, Gilead Sciences is also conducting clinical trials to evaluate its potential as a pre-exposure prophylaxis ( ) therapy.
In preclinical non-human primate studies, a low-dose or high-dose lenacapavir injection can reduce the risk of infection by 86% ( p=0.
0061 ) and 96% ( p=0.
0002 ), respectively.
In preclinical non-human primate studies, a low-dose or high-dose injection can reduce the risk of infection ( ) and ( ), respectively.
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75em;box-sizing:border-box ;overflow-wrap:break-word ;'>The drug hunter website pointed out that lenacapavir is a classic case of small molecule drug development, and I wish it more good news in the future clinical development and approval process.
The drug hunter website pointed out that lenacapavir is a classic case of small molecule drug development, and I wish it more good news in the future clinical development and approval process.
The drug hunter website pointed out that it is a classic case of small molecule drug development, and I wish it more good news in the future clinical development and approval process.

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