NPASS Compound

Natural Product: NPC303729

Natural Product ID	NPC303729
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	IVOMOUWHDPKRLL-ASCDQALMSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	25322948
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000289] Nucleosides, nucleotides, and analogues [CHEMONTID:0001506] Purine nucleotides [CHEMONTID:0001491] Cyclic purine nucleotides [CHEMONTID:0001502] 3',5'-cyclic purine nucleotides

The Chemical Classification was calculated by Classyfire, a software for chemical taxonomy calculation. Reference: DOI:10.1186/s13321-016-0174-y.

Chemical Representations

RDKit 3D 34 37 0 0 0 0 0 0 0 0999 V2000 -2.3221 0.3538 1.9799 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3378 0.5996 0.8843 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.8534 0.6690 -0.4873 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.4722 -0.7133 -1.0404 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.2463 -0.9931 -0.2607 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9774 -0.6045 -0.8808 N 0 0 0 0 0 0 0 0 0 0 0 0 1.2174 -0.2572 -2.1568 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5318 0.0353 -2.2911 N 0 0 0 0 0 0 0 0 0 0 0 0 3.1245 -0.1283 -1.0935 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4382 0.0341 -0.6743 C 0 0 0 0 0 0 0 0 0 0 0 0 5.4622 0.4460 -1.5631 N 0 0 0 0 0 0 0 0 0 0 0 0 4.7145 -0.2177 0.6311 N 0 0 0 0 0 0 0 0 0 0 0 0 3.7522 -0.6080 1.4800 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4938 -0.7641 1.0808 N 0 0 0 0 0 0 0 0 0 0 0 0 2.1563 -0.5302 -0.2004 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3724 -0.4027 0.9642 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4839 -1.5775 -0.5807 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1329 1.0121 -0.7052 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.2379 0.6692 0.4796 P 0 0 0 0 0 0 0 0 0 0 0 0 -5.4600 -0.0622 -0.0166 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6933 2.1301 1.2265 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4485 -0.3517 1.5753 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6880 1.3064 2.4226 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8731 -0.2166 2.8197 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8018 1.5571 1.1313 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2051 1.3803 -1.0818 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3808 -0.7185 -2.1214 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1883 -2.1047 -0.0883 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4382 -0.2361 -2.9052 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5613 -0.0107 -2.4790 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1058 1.2030 -1.2891 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9974 -0.8041 2.5222 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1027 -2.3651 -0.1246 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6707 2.2706 1.1723 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 2 0 5 16 1 0 4 17 1 0 3 18 1 0 18 19 1 0 19 20 2 0 19 21 1 0 19 22 1 0 22 1 1 0 16 2 1 0 15 6 1 0 15 9 1 0 1 23 1 0 1 24 1 0 2 25 1 1 3 26 1 6 4 27 1 6 5 28 1 1 7 29 1 0 11 30 1 0 11 31 1 0 13 32 1 0 17 33 1 0 21 34 1 0 M END

Standard InCHIKey	IVOMOUWHDPKRLL-ASCDQALMSA-N
Standard InCHI	InChI=1S/C10H12N5O6P/c11-8-5-9(13-2-12-8)15(3-14-5)10-6(16)7-4(20-10)1-19-22(17,18)21-7/h2-4,6-7,10,16H,1H2,(H,17,18)(H2,11,12,13)/t4-,6+,7+,10+/m1/s1
SMILES	C1[C@@H]2[C@@H]([C@@H]([C@@H](n3cnc4c(N)ncnc34)O2)O)OP(=O)(O)O1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	329.05	Volume:	264.297 ? Van der Waals volume.
Dense:	1.245	LogP:	-2.22 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.255 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-1.754 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	21.0
TPSA:	154.84 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.565	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.351	Fsp³:	0.5
MCE-18:	84.333 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.089	Fluc inhibitor:	0.001 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.056 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.015 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.121	Promiscuous compounds:	0.284

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.893	MDCK Permeability:	-5.158
Pgp-inhibitor:	0.001	Pgp-substrate:	0.269
PAMPA:	0.917 ? The experimental data for Peff was logarithmically transformed (logPeff). Molecules with log Peff values below 2.0 were classified as low-permeability (Category 0), while those with log Peff values exceeding 2.5 were classified as high-permeability (Category 1).	Human Intestinal Absorption (HIA):	0.092
20% Bioavailability (F20%):	0.175	30% Bioavailability (F30%):	0.418
50% Bioavailability (F50%):	0.665

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.136	MRP1:	0.58
Plasma Protein Binding (PPB):	21.68%	Volume Distribution (VD):	-0.562
Fu:	71.545% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.798
OATP1B3 inhibitor:	0.844	BCRP inhibitor:	0.005
BSEP inhibitor:	0.017

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.014	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.006
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.036
HLM stability:	0.05 ? Human liver microsomal (HLM) stability. Category 0: stable+ (HLM > 30 min); Category 1: unstable- (HLM ≤ 30 min). The output value is the probability of human liver microsomal instability, where a value closer to 1 indicates a higher likelihood of instability.

ADMET: Excretion

Clearance (CL):

2.992

Half-life (T1/2):

1.609

ADMET: Toxicity

hERG Blockers:	0.103	hERG Blockers (10um):	0.261
Human Hepatotoxicity (H-HT):	0.519	Drug-induced Liver Injury (DILI):	1.0
AMES Toxicity:	0.877	Rat Oral Acute Toxicity:	0.84
Maximum Recommended Daily Dose:	0.788	Skin Sensitization:	0.995
Carcinogencity:	0.685	Eye Corrosion:	0.0
Eye Irritation:	0.763	Respiratory Toxicity:	0.845
Drug-induced Neurotoxicity:	0.938	Ototoxicity:	0.054
Hematotoxicity:	0.654	Drug-induced Nephrotoxicity:	0.963
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.349
A549 Cytotoxicity:	0.131	Hek293 Cytotoxicity:	0.47
BCF:	0.073 ? Bioconcentration factors are used for considering secondary poisoning potential and assessing risks to human health via the food chain. The unit is -log10[(mg/L)/(1000*MW)].	IGC50:	2.413 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	3.876 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.283 ? 96 hour fathead minnow LC50. The unit of LC50FM is -log10[(mg/L)/(1000*MW)].

Species Source

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO28626	Isodon rubescens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25590529]
NPO5986	Ziziphus jujuba	Species	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[27617953]
NPO5986	Ziziphus jujuba	Species	Rhamnaceae	Eukaryota	Roots	n.a.	n.a.	PMID[28257196]
NPO5986	Ziziphus jujuba	Species	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO28626	Isodon rubescens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO5986	Ziziphus jujuba	Species	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO23604	Fructus choerospondiatis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[HerDing]
NPO23604	Fructus choerospondiatis	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[TCMID]
NPO5986	Ziziphus jujuba	Species	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28626	Isodon rubescens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO5986	Ziziphus jujuba	Species	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO5986	Ziziphus jujuba	Species	Rhamnaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28626	Isodon rubescens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO28626	Isodon rubescens	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]

Note for Reference:
In addition to directly collecting NP source organism data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated them from below databases:
☉ UNPD: Universal Natural Products Database [PMID: 23638153].
☉ StreptomeDB: a database of streptomycetes natural products [PMID: 33051671].
☉ TM-MC: a database of medicinal materials and chemical compounds in Northeast Asian traditional medicine [PMID: 26156871].
☉ TCM@Taiwan: a Traditional Chinese Medicine database [PMID: 21253603].
☉ TCMID: a Traditional Chinese Medicine database [PMID: 29106634].
☉ TCMSP: The traditional Chinese medicine systems pharmacology database and analysis platform [PMID: 24735618].
☉ HerDing: a herb recommendation system to treat diseases using genes and chemicals [PMID: 26980517].
☉ MetaboLights: a metabolomics database [PMID: 27010336].
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

NP Quantity Composition/Concentration

Organism ID	Organism Name	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP quantitative records for specific NP domains (e.g., NPS from foods or herbs) from domain-specific databases. These databases include:
☉ DUKE: Dr. Duke's Phytochemical and Ethnobotanical Databases.
☉ PHENOL EXPLORER: is the first comprehensive database on polyphenol content in foods [PMID: 24103452], its homepage can be accessed at here.
☉ FooDB: a database of constituents, chemistry and biology of food species [www.foodb.ca].

Biological Activity

Molecular-level activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vitro activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

In vivo activity

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference

Experimental ADME

Experiment Model	Experiment Tissue	ADME Type	ADME Relation	ADME Value	ADME Unit	Reference

Experimental Toxicity

Quantitative toxicity

Experiment Model	Experiment Organism	Toxicity Type	Toxicity Relation	Toxicity Value	Toxicity Unit	Reference

Common Abbreviations:
LC: Lethal Concentration; LD: Lethal Dose; LT:Lethal Time; NOAEL: No-observed-adverse-effect Level; BMDL: Benchmark Dose Lower Confidence Limit; BMD: Benchmark Dose; BMC:Benchmark Concentration; LOAEL: Lowest Observed Adverse Effect Level; RfD:Reference Dose; RfC:Reference Concentration; MRL: Minimal Risk Level; MEG: Maximum Exposure Guideline; PAC: Protective Action Criteria

Categorical toxicity labels

Hepatotoxicity	Carcinogenicity	Mutagenicity	Cardiotoxicity	Respiratory Toxicity	Eye Irritation	Endocrine Disruption

Note for Reference:
In addition to directly collecting NP quantitative data from primary literature (where reference will provided as NCBI PMID or DOI links), NPASS also integrated NP toxicity records from domain-specific databases. These databases include:
☉ ToxValDB: a curated database that compiles quantitative toxicity values for chemicals from diverse public sources to support toxicological research and risk assessment.
☉ TOXRIC: a comprehensive, free-to-access, online database providing toxicological/feature data. The toxicity labels are retrieved from this database. [PMID: 36400569]

Chemically structural similarity

Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes approximately 50,000 NPs with experimentally-derived bioactivity available in NPASS)

Similarity is measured using the Tanimoto coefficient (Tc) , which compares the binary fingerprints of two molecules. Tc is calculated as the intersection divided by the union of '1' bits in the fingerprints, ranging from 0 to 1, with 1 indicating highest similarity.

● The left chart: Distribution of similarity level between NPC303729 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	34919
0.1-0.2	14767
0.2-0.3	67
0.3-0.4	33
0.4-0.5	35
0.5-0.6	20
0.6-0.7	11
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC302778
1.0	High Similarity	NPC329404
1.0	High Similarity	NPC212551
0.7727	Intermediate Similarity	NPC164952
0.7246	Intermediate Similarity	NPC224076
0.6618	Remote Similarity	NPC85689
0.6528	Remote Similarity	NPC324198
0.6528	Remote Similarity	NPC326529
0.6528	Remote Similarity	NPC319100
0.6438	Remote Similarity	NPC130586
0.6267	Remote Similarity	NPC174802
0.6197	Remote Similarity	NPC185991
0.6197	Remote Similarity	NPC321814
0.6184	Remote Similarity	NPC481375
0.6184	Remote Similarity	NPC606410
0.6104	Remote Similarity	NPC323091
0.5914	Remote Similarity	NPC189261
0.5846	Remote Similarity	NPC317821
0.5783	Remote Similarity	NPC326082
0.5769	Remote Similarity	NPC161224
0.5714	Remote Similarity	NPC136349
0.5714	Remote Similarity	NPC219313
0.5696	Remote Similarity	NPC316618
0.5676	Remote Similarity	NPC121222
0.5672	Remote Similarity	NPC156461
0.5672	Remote Similarity	NPC107374
0.5672	Remote Similarity	NPC600382
0.5672	Remote Similarity	NPC612067
0.5588	Remote Similarity	NPC229974
0.527	Remote Similarity	NPC211025
0.5263	Remote Similarity	NPC328479
0.5176	Remote Similarity	NPC478860
0.5143	Remote Similarity	NPC209525
0.5143	Remote Similarity	NPC161659
0.5125	Remote Similarity	NPC324484
0.507	Remote Similarity	NPC609472

Similar Clinical/Approved Drugs

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules.

● The left chart: Distribution of similarity level between NPC303729 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5958
0.1-0.2	3057
0.2-0.3	63
0.3-0.4	45
0.4-0.5	18
0.5-0.6	5
0.6-0.7	2
0.7-0.8	1
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.7246	Intermediate Similarity	NPD169	Phase 2
0.6267	Remote Similarity	NPD339	Phase 2
0.6197	Remote Similarity	NPD283	Phase 4
0.5714	Remote Similarity	NPD548	Clinical (unspecified phase)
0.5672	Remote Similarity	NPD249	Phase 4
0.5672	Remote Similarity	NPD250	Phase 4
0.5455	Remote Similarity	NPD338	Approved
0.5395	Remote Similarity	NPD4171	Clinical (unspecified phase)

Bioactivity similarity

Similar Natural Products in NPASS

Similarity level is defined by Bioactivity similarity was calculated based on bioactivity descriptors of compounds. The bioactivity descriptors were calculated by a recently developed AI algorithm Chemical Checker (CC) [Nature Biotechnology, 38:1087–1096, 2020; Nature Communications, 12:3932, 2021], which evaluated bioactivity similarities at five levels:
☉ A: chemistry similarity;
☉ B: biological targets similarity;
☉ C: networks similarity;
☉ D: cell-based bioactivity similarity;
☉ E: similarity based on clinical data.
Those 5 categories of CC bioactivity descriptors were calculated and then subjected to manifold projection using UMAP algorithm, to project all NPs on a 2-Dimensional space. The current NP was highlighted with a small circle in the 2-D map. Below figures: left-to-right, A-to-E.

A: chemistry similarity

B: biological targets similarity

C: networks similarity

D: cell-based bioactivity similarity

E: similarity based on clinical data