About

Richard Hong is a Clinical Assistant Professor in Radiology at Stanford University and is affiliated with the Center for Artificial Intelligence in Medicine & Imaging (AIMI). His work focuses on the application of artificial intelligence in the field of medicine and imaging, contributing to the advancement of AI-driven healthcare solutions. As part of AIMI, he is involved in research initiatives aimed at integrating AI technologies into clinical practice, enhancing diagnostic accuracy, and improving patient outcomes. His role encompasses both research and education, supporting the development of innovative AI tools and training the next generation of healthcare professionals in AI methodologies.

Research topics

• Medicine
• Computer Science
• Organic chemistry
• Internal medicine
• Chemistry
• Pharmacology
• Dentistry
• Orthodontics
• Materials science
• Combinatorial chemistry
• Biochemistry
• Surgery

Selected publications

• Data from Expanding the Repertoire for “Large Small Molecules”: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers

  2023-04-03

  preprintOpen access

  <div>Abstract<p>Since gaining approval for the treatment of chronic lymphocytic leukemia (CLL), the BCL-2 inhibitor venetoclax has transformed the treatment of this and other blood-related cancers. Reflecting the large and hydrophobic BH3-binding groove within BCL-2, venetoclax has significantly higher molecular weight and lipophilicity than most orally administered drugs, along with negligible water solubility. Although a technology-enabled formulation successfully achieves oral absorption in humans, venetoclax tablets have limited drug loading and therefore can present a substantial pill burden for patients in high-dose indications. We therefore generated a phosphate prodrug (<b>3</b>, ABBV-167) that confers significantly increased water solubility to venetoclax and, upon oral administration to healthy volunteers either as a solution or high drug-load immediate release tablet, extensively converts to the parent drug. Additionally, ABBV-167 demonstrated a lower food effect with respect to venetoclax tablets. These data indicate that beyond-rule-of-5 molecules can be successfully delivered to humans via a solubility-enhancing prodrug moiety to afford robust exposures of the parent drug following oral dosing.</p></div>

  PublisherDOI

• Supplementary Data from Expanding the Repertoire for “Large Small Molecules”: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers

  2023-04-03

  preprintOpen access

  <p>1. Measured pKa values of ABBV-167 (Table S1. Ionization constants of ABBV-167) 2. Preparation of ABBV-167 on large scale (Scheme S1: Synopsis of GMP synthesis of ABBV-167) 3. Preparation of clinical ABBV-167 drug supply 4. Animal pharmacokinetics (Table S2. Single dose pharmacokinetics of prodrug 3 and parent venetoclax in mouse and dog after IV dosing of prodrug 3. Table S3. Single dose pharmacokinetics of 3 after oral dosing in mouse and dog. Table S4. Single dose pharmacokinetics of parent venetoclax in mouse and dog after oral dosing of 3.) 5. Clinical study (Study design, Pharmacokinetic and statistical analysis, Safety and tolerability assessments, Clinical pharmacokinetic results, Table S5. Effect of prodrug and food on venetoclax bioavailability, Safety results) 6. Crystallography methods (Protein preparation. BCL-2 ABBV-167 complex crystallization. X-ray structure determination. Table S6. Diffraction data collection and refinement statistics for BCL-2 in complex with ABBV-167 (PDB code 7LHB))</p>

  PublisherDOI

• Complex Therapeutic Process due to Diagnostic Error in the Periapical Fibro-Osseous Lesion of Mandibular First Molar. A Case Report with Successful Implant Placement

  Annals of Case Reports · 2023 · 1 citations

  • Computer Science
  • Dentistry
  • Medicine

  Cemento-osseous dysplasia (COD) present radiographically as radiolucent lesions that are frequently misdiagnosed as endodontic lesions.The following case report involves a 42-year-old female that was treated for a molar endodontic lesion.The typically benign lesion, post endodontic therapy caused pain and chewing discomfort.The tooth was extracted a year later and biopsy samples confirmed the initial lesion was focal cemento osseous dysplasia (FCOD).The site was rehabilitated with dental implants and supplemented with bone graft material.The histological evidence of the extraction site revealed osteoporotic large bony marrow spaces with an inflammatory cell infiltrate, supplemented with cells of hematopoietic origin.Typically, sites that have abnormal bone quality, with confirmed diagnosis of cemento-osseous dysplasia are not considered ideal sites to receive implant placements.The present case report demonstrates a sequence of events for the management of FCOD in the posterior mandible with successful implant and bone graft treatment.Typically asymptomatic, FCOD benign lesions are not ideal candidates for implant placement, the following case reports depicts favorable outcomes in terms of osteointegration of the dental implant and subsequent oral rehabilitation for improved function.

  PublisherOA PDFDOI

• Supplementary Data from Expanding the Repertoire for “Large Small Molecules”: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers

  2023-04-03

  preprintOpen access

  <p>1. Measured pKa values of ABBV-167 (Table S1. Ionization constants of ABBV-167) 2. Preparation of ABBV-167 on large scale (Scheme S1: Synopsis of GMP synthesis of ABBV-167) 3. Preparation of clinical ABBV-167 drug supply 4. Animal pharmacokinetics (Table S2. Single dose pharmacokinetics of prodrug 3 and parent venetoclax in mouse and dog after IV dosing of prodrug 3. Table S3. Single dose pharmacokinetics of 3 after oral dosing in mouse and dog. Table S4. Single dose pharmacokinetics of parent venetoclax in mouse and dog after oral dosing of 3.) 5. Clinical study (Study design, Pharmacokinetic and statistical analysis, Safety and tolerability assessments, Clinical pharmacokinetic results, Table S5. Effect of prodrug and food on venetoclax bioavailability, Safety results) 6. Crystallography methods (Protein preparation. BCL-2 ABBV-167 complex crystallization. X-ray structure determination. Table S6. Diffraction data collection and refinement statistics for BCL-2 in complex with ABBV-167 (PDB code 7LHB))</p>

  PublisherDOI

• Data from Expanding the Repertoire for “Large Small Molecules”: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers

  2023-04-03

  preprintOpen access

  <div>Abstract<p>Since gaining approval for the treatment of chronic lymphocytic leukemia (CLL), the BCL-2 inhibitor venetoclax has transformed the treatment of this and other blood-related cancers. Reflecting the large and hydrophobic BH3-binding groove within BCL-2, venetoclax has significantly higher molecular weight and lipophilicity than most orally administered drugs, along with negligible water solubility. Although a technology-enabled formulation successfully achieves oral absorption in humans, venetoclax tablets have limited drug loading and therefore can present a substantial pill burden for patients in high-dose indications. We therefore generated a phosphate prodrug (<b>3</b>, ABBV-167) that confers significantly increased water solubility to venetoclax and, upon oral administration to healthy volunteers either as a solution or high drug-load immediate release tablet, extensively converts to the parent drug. Additionally, ABBV-167 demonstrated a lower food effect with respect to venetoclax tablets. These data indicate that beyond-rule-of-5 molecules can be successfully delivered to humans via a solubility-enhancing prodrug moiety to afford robust exposures of the parent drug following oral dosing.</p></div>

  PublisherDOI

• Pharmaceutical Development Challenges in a Beyond Rule of Five Prodrug: Case Study of ABBV-167, Phosphate Prodrug of Venetoclax

  Molecular Pharmaceutics · 2023 · 4 citations

  1st authorCorresponding
  • Chemistry
  • Materials science
  • Pharmacology

  ABBV-167, a phosphate prodrug of BCL-2 inhibitor venetoclax, was recently progressed into the clinic as an alternative means of reducing pill burden for patients in high-dose indications. The dramatically enhanced aqueous solubility of ABBV-167 allowed for high drug loading within a crystalline tablet and, when administered in phase I clinical study, conferred venetoclax exposure commensurate with the equivalent dose administered as an amorphous solid dispersion. In enabling the progression into the clinic, we performed a comprehensive evaluation of the CMC development aspects of this beyond the rule of five (bRo5) prodrug. Adding a phosphate moiety resulted in excessively complex chemical speciation and solid form landscapes with significant physical-chemical stability liabilities. A combination of experimental and computational methods including microelectron diffraction (MicroED), total scattering, tablet colorimetry, finite element, and molecular dynamics modeling were used to understand CMC developability across drug substance and product manufacture and storage. The prodrug's chemical structural characteristics and loose crystal packing were found to be responsible for the loss of crystallinity during its manufacturing, which in turn led to high solid-state chemical reactivity and poor shelf life stability. The ABBV-167 case exemplifies key CMC development challenges for complex chemical matter such as bRo5 phosphate prodrugs with significant ramifications during drug substance and drug product manufacturing and storage.

  PublisherDOI

• Intralipid fails to rescue bupivacaine-induced cardiotoxicity in late-pregnant rats

  Frontiers in Medicine · 2022-08-12

  articleOpen access

  Background Females routinely receive bupivacaine for obstetric and regional anesthesia. An accidental overdose of bupivacaine can result in cardiotoxicity and cardiac arrest. Intralipid (ILP) rescues bupivacaine-induced cardiotoxicity in male rats. However, bupivacaine cardiotoxicity and ILP rescue have not been studied in non-pregnant and late-pregnant female rats. Here, we tested the hypothesis that an appropriate dose of ILP would rescue non-pregnant and late-pregnant rats from bupivacaine-induced cardiotoxicity. Methods Non-pregnant ( n = 6) and late-pregnant ( n = 7) female rats received intravenous bupivacaine (10-mg/kg bolus) to induce asystole. Resuscitation with 20% ILP (5-ml/kg actual body weight, single bolus, and 0.5-ml/kg/min maintenance) and chest compressions were continued for 10-min. Serial heart rate (HR), left ventricular ejection-fraction (LVEF%), and LV-fractional shortening (LVFS%) were recorded at baseline and 10-min after bupivacaine-induced cardiac arrest. Data are mean ± SD followed by 95% CI. P -values < 0.05 were considered statistically significant. Results All rats developed cardiac arrest within a few seconds after bupivacaine. All non-pregnant rats were successfully rescued by ILP, with a HR of 280 ± 32 bpm at baseline vs. 212 ± 18 bpm at 10-min post ILP ( p < 0.01), LVEF of 70 ± 6% vs. 68 ± 5% ( p = ns), and LVFS of 41 ± 5% vs. 39 ± 4% ( p = ns). Interestingly, 6 out of 7 late-pregnant rats did not recover with ILP. Baseline HR, LVEF and LVFS for late-pregnant rats were 330 ± 40 bpm, 66 ± 5% and 38 ± 4%, respectively. At 10-min post ILP, the HR, LVEF, and LVFS were 39 ± 102 bpm ( p < 0.0001), 8 ± 22% ( p < 0.0001), and 5 ± 12% ( p < 0.001), respectively. Conclusions ILP successfully rescued bupivacaine-induced cardiac arrest in non-pregnant rats, but failed to rescue late-pregnant rats.

  PublisherOA PDFDOI

• Issue Information

  Journal of Dental Education · 2020-05-01

  paratextOpen access
  PublisherOA PDFDOI

• Immunodeficiency Diseases

  CRC Press eBooks · 2020 · 2 citations

  1st authorCorresponding
  • Medicine

  This chapter discusses the physiologic requirements for the development of the normal immune response. It describes how a failure of these processes as a consequence of genetic or other faults can lead to the diseases observed. The chapter reviews symptomatology and treatment of the immunologic deficiency states. Glycoconjugates are regularly found in the plasma membranes of mammalian cells. They play essential roles in cell-cell and cell-ligand interactions. T cells use the major histocompatibility complex products to recognize and respond to antigenic stimuli. The major distinguishing characteristic of immune responses is specificity. The specificity is directed against the agent that induced the immune response, and specificity is attained through the lymphocyte surface receptors. A number of factors in the fluid phase are important in controlling the cellular interactions of the immune response. The targeting of these factors and their transmembrane effects is facilitated by specific cell surface receptors.

  PublisherDOI

• Case 3: Rapidly Expanding Neck Mass Leading to Cardiopulmonary Arrest in a 14-year-old Boy

  Pediatrics in Review · 2020-01-01

  article

  1. Stanley Lee, MD* 2. Ahmed Aly, MBBS* 3. Paayal Bhakta, MD* 4. Karthikeyan Parameswaran, MBBS* 5. Valeriy Chorny, MD* 6. Rohit Pinto, MD* 7. Jianying Zeng, MD† 8. Richard Hong, MD‡ 9. Melvyn Braiman, MD* 1. *Department of Pediatrics, 2. †Department of Pathology, and 3. ‡Department of Radiology, SUNY Downstate Medical Center and Kings County Hospital Center, Brooklyn, NY A 14-year-old boy is transferred from an outside hospital with a 1-day history of severe left upper neck swelling and pain without any known precipitating factors. Three years ago the patient had a similar episode: a painful left neck mass was diagnosed as lymphadenitis and treated with amoxicillin without sequelae. In the emergency department, vital signs and a complete blood count are within normal limits. The mass is soft and tender to palpation, measuring 1.0 × 1.5 cm. A computed tomographic (CT) scan with contrast reveals an expansile lesion stemming from the left aspect of the hyoid bone compressing the trachea (Fig 1). The ENT team performs a bedside laryngoscopy and confirms a rightward tracheal deviation and compression. Figure 1. Expansile lesion of the hyoid bone causing a rightward tracheal deviation. A computed tomographic scan of the neck revealing a 1.3-cm lesion from the left hyoid bone (blue arrow) with an associated 11.2-cm soft tissue mass expanding through the thoracic outlet. The lesion led to a rightward tracheal deviation and compression (red arrow). On admission to the inpatient unit, the patient is alert, oriented, and in mild distress due to pain, but his vital signs remain within normal limits. The neck mass remains very tender to palpation and has expanded to 4.0 × 5.0 cm on physical examination, a few hours after the initial measurement. His neck has limited movement, and there are no signs of respiratory distress, stridor, drooling, or retractions. He is able to speak in full sentences. He has some difficulty in swallowing solids but is tolerating liquids. He is started on …

  PublisherDOI

Frequent coauthors

• Paul G. Quie

  1227 shared

• Erwin W. Gelfand

  University of Colorado Denver

  1226 shared

• Philip Sunshine

  Stanford University

  1225 shared

• Drs Philip

  Niagara University

  1225 shared

• Daniel Halpern

  1225 shared

• Robert G. Schwartz

  1225 shared

• Ken Schonberg

  Children's Hospital of Michigan

  1225 shared

• Howard Banquet

  University of Tennessee at Knoxville

  1225 shared