This privacy policy describes the types of personal information collected through NATSARpharmaceuticals.com (“website”) and how NATSAR (“we, our, us”) uses, shares, and protects that information.
This privacy policy applies to the personal information NATSAR collects on this website (NATSARpharmaceuticals.com).
We may collect and store personal information that our website visitors voluntarily provide when they contact us through this website. Personal information may include the visitor’s name, email address, telephone number, or home address. We use this information to respond to visitors' requests and questions.
Cookies are bits of text that are placed on a website visitor’s computer hard drive or Internet-connected device. Cookie technology holds information that a site may need to personalize a visitor’s experience. Cookies may also be used for security purposes and to gather statistical data about how visitors navigate and use the website, such as which pages they visit, what they download, and the paths they take to find the website and move from page to page.
NATSAR uses cookies to identify visitors and to track their usage of our website. Visitors who do not wish to have cookies placed on their computers may disable cookies within their browser before using our website.
We do not sell or otherwise disclose personal information we collect about website visitors, except as described herein or otherwise disclosed to visitors at the time the data are collected.
We may share information provided by our website visitors with service providers we have retained to perform services on our behalf including, without limitation, hosting or operating this website, carrying out visitors’ requests, responding to visitors’ inquiries, and analyzing data. By contract we require these service providers to appropriately safeguard the privacy and security of personal information they process on our behalf.
We may disclose information about a visitor, as compelled or required by law, to law enforcement authorities or other government officials, to protect or defend our legal rights, or to investigate, prevent, or take action regarding illegal activities, suspected fraud, or violations of our terms of use for this website or other applicable policies.
We also reserve the right to transfer personal information we have collected through our website in the event that we sell or transfer all or a portion of our business.
The security of personal information is important to us, and we are committed to using reasonable measures to protect the personal information we may collect. However, due to the inherently open nature of the Internet, we cannot guarantee that communications between our website visitors and us, or the information stored on this website, are absolutely secure.
This website may provide links to other websites for our visitors’ convenience and information. These websites may operate independently from us. NATSAR is not responsible for the privacy or security practices of these sites or content contained therein. We strongly encourage visitors to review these sites to better understand their procedures for collecting, using, and disclosing personal information.
This privacy policy applies only to information collected through our website and not to information collected offline.
We do not knowingly collect or solicit personally identifiable information from or about children under the age of 13.
By using this website, visitors consent to the processing of their personal information as described in this privacy policy.
We reserve the right to change or add to this privacy policy from time to time and will post any revisions on this website. We will indicate at the bottom of the privacy policy when it was most recently updated. We encourage visitors to check back often to review the latest version.
If you have any questions, concerns, or complaints regarding this privacy policy or privacy issues related to the website, you can contact us at vraman@natsarpharmaceuticals.com
Privacy Policy Effective Date: Sept. 15, 2016
NATSAR provides this website for visitors’ personal informational, educational, and entertainment use. These terms of use governing access to and use of this website should be read carefully before using the website. Within these terms of use, “we” and “our” refer to NATSAR, and “you” and “your” refer to any individual, company, or legal entity that accesses or otherwise uses this website (NATSARpharmaceuticals.com).
By using the website, you agree to be legally bound by these terms of use and you agree to the processing of your personal data in accordance with our privacy policy. If you do not agree with these terms of use or our privacy policy, you should not use the website.
These terms of use may be amended by NATSAR, in its sole discretion, at any time without notice to you. Amendments to the terms of use shall be effective upon posting. By continuing to access or use this website, you will be deemed to have accepted such amendments. You are advised to regularly review any applicable terms and conditions. NATSAR reserves the right to discontinue or make changes or updates with respect to the website or its content at any time without notice.
The content appearing on this website may include technical, typographical, or photographic errors. We do not warrant that any of the content on the website is accurate, complete, or current. We may make changes to the website content at any time without notice. We do not, however, make any commitment to update the content.
NATSAR grants permission to temporarily download the materials (information or software) on this website for personal, noncommercial viewing only. This is the grant of a license, not a transfer of title. Under this license you may not:
From time to time, the website may include links to third-party websites. These links are provided for your convenience only and do not signify that we endorse such third-party websites. We do not review such third-party websites. In accessing them, you acknowledge and agree that:
NATSAR recommends that you make yourself aware of and read the legal and privacy notices of all other websites that you visit.
Except as expressly provided in these terms of use, this website is made available to you on an “as is” basis. We disclaim and do not accept any liability to you with respect to the website, your use of it, or otherwise. It is your responsibility to ensure that the website is suitable for your intended purposes. We make no warranties, expressed or implied, and hereby disclaim and negate all other warranties, including without limitation implied warranties or conditions of merchantability, fitness for a particular purpose, and noninfringement of intellectual property or other violation of rights.
We give no warranty:
You also acknowledge and agree that the operation of the website is dependent on the proper and effective functioning of the Internet and other third-party equipment and services, and that we do not guarantee and will not be liable for these in any way.
We will not be liable to you for any special, indirect, or consequential losses or damages, or any loss of data, profits, revenues, business, or goodwill. Because some jurisdictions do not allow limitations on implied warranties or limitations of liability for consequential or incidental damages, these limitations may not apply to you.
TO THE MAXIMUM EXTENT PERMITTED BY APPLICABLE LAW, YOU EXPRESSLY WAIVE ALL CLAIMS AGAINST NATSAR AND ITS AFFILIATES AND THEIR OFFICERS, DIRECTORS, EMPLOYEES, SHAREHOLDERS, SUPPLIERS, AND PROGRAMMERS THAT MAY ARISE FROM YOUR ACCESS OR USE OF THIS WEBSITE.
You agree to indemnify, defend, and hold harmless NATSAR and its affiliates against all claims, demands, causes of action, losses, expenses, damages, and costs, including any reasonable attorneys' fees, resulting or arising from or relating to:
If you have a dispute with one or more users, you release NATSAR and its affiliates from claims, demands, or damages (actual and consequential) of every kind and nature, known and unknown, arising out of or in any way connected with such disputes.
The intellectual property rights in this website and copyright in all material stored, displayed, and accessible on the website are either owned by us or duly licensed by third parties. All such rights are reserved.
These terms of use and any dispute or claim arising out of or in connection with these terms of use or their subject matter (including noncontractual disputes or claims) are subject to the laws of the State of Maryland without regard to its conflict of law provisions.
If any provision of these terms of use is held to be unlawful, void, or for any reason unenforceable by a court of competent jurisdiction, then the invalid or unenforceable provision shall be replaced by a valid, enforceable provision that most closely matches the intent of the original provision, and the validity and enforceability of any remaining provisions shall not be affected.
The failure of NATSAR and its affiliates to enforce any part of these terms of use shall not constitute a waiver of such term or provision, and shall not be considered a waiver or limit of NATSAR’s right thereafter to insist on strict adherence to that term or any other provision of these terms of use.
Terms of Use Effective Date: Sept. 15, 2016
Natsar Pharmaceuticals is an applied research and drug development company focused on the development of novel treatments for cancer and other diseases. In our quest to characterize cellular pathways that are essential for the oncogenic state, we have focused on helicases which are dysregulated in many cancer types.
One such helicase is DDX3, which is overexpressed in many cancer types and has been associated with lower survival in lung cancer patients. We have synthesized a DDX3 inhibitor, RK‐33, which can potentially be used in cancer treatment. Binding of RK‐33 to DDX3 impedes the function of DDX3, resulting in activation of cell death pathways, inhibition of the Wnt‐signaling pathway, and abrogation of non‐homologous end‐joining (NHEJ) activity. In combination with radiation, synergistic cell death effects have been observed both in vitro and in multiple preclinical cancer models. We are currently moving this synthesized compound into clinical trials.
Professor, Johns Hopkins University, Founder & Director, NATSAR
ACTING CHIEF CLINICAL OFFICER
Based on our identification of an RNA helicase, DDX3, which is overexpressed in many cancer types and has been associated with lower survival in lung cancer patients, we have designed a first‐in‐class small molecule inhibitor, RK‐33, which binds to DDX3 and abrogates its activity. Inhibition of DDX3 by RK‐33 causes G1 cell cycle arrest, induces apoptosis, and promotes radiation sensitization in DDX3‐overexpressing cells. Overall, inhibition of DDX3 by RK‐33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for cancer therapy.
DDX3 is a member of the DEAD‐box family which is involved in a number of cellular processes such as transcription, RNA splicing, mRNA export, and translation initiation (Lorsch, 2002; Rocak & Linder, 2004). DDX3 has also been associated with cancer biogenesis (Hu et al, 2004). We identified DDX3 in a microarray screen of breast cancer cells exposed to cigarette smoke and demonstrated its role in cancer progression (Botlagunta et al, 2008).
DDX3 promotes proliferation and cellular transformation (Hu et al, 2004; Shih et al, 2007; Lee et al, 2008), has anti‐apoptotic properties (Li et al, 2006; Sun et al, 2008, 2011), modulates cell adhesion and motility (Chen et al, 2014), and responds to hypoxia via HIF‐1α (Botlagunta et al, 2011; Bol et al, 2013).
Also, recent evidence has identified that DDX3 acts as an allosteric activator of casein kinase 1 in the Wnt/β‐catenin pathway (Cruciat et al, 2013). Initially, the Wnt/β‐catenin pathway was described in colon cancer. Activating mutations of DDX3 were also shown to be involved in pathogenic Wnt pathway activation in medulloblastoma (Jones et al, 2012; Pugh et al, 2012; Robinson et al, 2012) and chronic lymphatic leukemia (CLL) (Wang et al, 2011). Recently, it has been shown that activated Wnt signaling predicts decreased survival in lung cancer patients (Xu et al, 2011; Shapiro et al, 2013) and decreases sensitivity to radiation therapy (Woodward et al, 2007; Zhang et al, 2010).
RK‐33 binds to DDX3 and abrogates its activity, causing G1 cell cycle arrest, inducing apoptosis, and promoting radiation sensitization in DDX3‐overexpressing cells. Mechanistically, loss of DDX3 function either by shRNA or by RK‐33 impaired Wnt signaling through disruption of the DDX3–β‐catenin axis and inhibited non‐homologous end joining—the major DNA repair pathway in mammalian somatic cells. Inhibition of DDX3 by RK‐33 promotes tumor regression, thus providing a compelling argument to develop DDX3 inhibitors for cancer therapy. RK‐33 combined with radiation therapy has been shown to induce tumor regression in lung cancer models, with no toxicity at the therapeutic dose.
Our clinical development plan will include sarcoma and breast cancer. We will use a novel, biomarker-driven Phase I trial design. Enrollment will be limited to patients with DDX3 expression demonstrated on a pre-treatment tumor biopsy. Dose finding will be based on a Continual Reassessment Model, and there will be a sarcoma-only expansion cohort at the recommended Phase II dose to obtain preliminary evidence of efficacy, increased data on toxicity, and to allow pharmacodynamic and pharmacokinetic studies. Subsequent clinical development is planned in multiple solid tumors including prostate, and medulloblastoma, and in combination with radiation.
Read more about Natsar below.
The latest publication from Dr. Venu Raman's lab indicates that DDX3 is a relevant clinical target in breast cancer bone metastasis and that RK-33 can be a safe and effective treatment for these patients.
Dr. Venu Raman is a professor with @Hopkins_Rad and has been developing an exciting drug called RK-33 that is nearing clinical trials and will be a first-in-class cancer treatment with the ability to mitigate many other diseases including SARS-CoV-2 and RSV. #FacultyFriday
Today's press release by Johns Hopkins Medicine about our work with RK-33.
DDX3 is a host DEAD-box RNA helicase that is usurped by SARS-CoV-2 for virus production. When the researchers inhibited DDX3 with a small molecule inhibitor, RK-33, viral load was reduced in four isolates of SARS-CoV-2 (including the Delta variant) by one to three log orders in Calu-3 cells. The data presented supports the use of RK-33 as a host targeting antiviral (HTA) strategy to control SARS-CoV-2 infection, irrespective of its mutational status, in humans.
Target Update - A newly released paper by Rao, et al looked at the impact of DDX3 inhibition on inducing selective cell death in HIV infected cells . The group demonstrated that Natsar's DDX3 inhibitor, RK-33, was able to bring HIV cells out of latency and induce apoptosis, thereby reducing the total virus reservoir.
The authors conclude, "DDX3 inhibitors are especially interesting as a potential therapeutic class of compounds for use in curative strategies against HIV-1 because they target multiple steps of the HIV-1 life cycle."
A recent non-clinical study by Fimia et al. (Proteomic Analysis Identifies the RNA Helicase DDX3 as a Host Target Against SARS-CoV2 Infection) in the journal Antiviral Research adds further support to the role of DDX3 as a host target against SARS-CoV2 infection. The study also demonstrated that inhibition of DDX3 by RK-33 significantly reduced SARS-CoV-2 replication in cell culture.
January 2021 – A new review article “Targeting host DEAD-box RNA helicase DDX3X for treating viral infections” is published in Antiviral Research by Natsar's founder and Professor of Radiology and Oncology at Johns Hopkins School of Medicine, Dr. Venu Raman. Natsar’s small molecule, RK-33 has been demonstrated to effectively abrogate virion production in both + ssRNA (DENV, WNV, and ZIKA) and -ssRNA (RSV and hPIV-3) infections.
In pancreatic CSCs, PAF1 forms a sub-complex that regulates expression of genes that control stem cell features. Knockout of PAF1 reduced the ability of pancreatic tumors to develop and progress in mice and numbers of CSCs.
In this paper by Vellky et al. the authors have demonstrated that high DDX3 expression downregulates androgen receptor (AR) expression, leading to the generation of castration-resistant prostate cancer phenotypes. Interestingly, the authors showed that treatment with RK-33, both in vitro and in vivo, deregulates DDX3 expression, thus sensitizing the castration-resistant prostate cancer cells to AR-signaling inhibitors. Significance of this finding is that use of RK-33, in a clinical setting, for castration-resistant prostate cancer treatment is a strategy that can be exploited both to decrease the generation of castration-resistant prostate cancers as well as potentially prevent the recurrence of castration-resistant prostate cancer.
In this week's Cancer Matters podcast, Dr. Bill Nelson speaks with Dr. Venu Raman about his work to develop a cancer drug targeting a gene that stabilizes tumors.
Raman’s drug discovery began with research to understand the effect of secondhand smoke on breast cancer. It led him and his team to develop a first in-class drug called RK-33. Countless hours in the lab and hundreds of experiments and assays later, Raman and his team have developed and patented a small molecule inhibitor of the DDX3 gene, an exciting first-in-class pharmaceutical.