NPASS Compound

Natural Product: NPC258342

Natural Product ID	NPC258342
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	JAKPEFAGBAKNJU-BFMVXSJESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	5318154
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002105] Glycosyl compounds [CHEMONTID:0004165] Phenolic glycosides

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 52 54 0 0 0 0 0 0 0 0999 V2000 1.0061 1.0691 1.8215 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3284 0.6839 1.6460 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0183 0.9007 0.4729 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3362 1.5356 -0.5770 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9662 1.9149 -0.4145 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6464 1.6908 0.7689 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0582 2.1166 0.9070 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8762 1.0555 0.4917 O 0 0 0 0 0 0 0 0 0 0 0 0 5.2472 1.0701 0.4749 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8280 2.1278 0.8660 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0211 -0.0915 0.0222 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3454 -1.2067 -0.3891 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0307 -2.3063 -0.8168 C 0 0 0 0 0 0 0 0 0 0 0 0 7.4207 -2.3556 -0.8582 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0956 -1.2264 -0.4415 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3827 -0.1068 -0.0058 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0718 -3.5002 -1.3024 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0453 1.7442 -1.7459 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3194 0.5270 0.2968 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1807 -0.1120 1.1994 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3137 0.8355 1.5132 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2908 1.0257 0.4087 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0200 -0.0701 -0.6312 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8133 -1.3187 0.1979 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.1625 -2.5680 -0.5824 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.5002 -2.4077 -0.9987 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5387 -1.3166 0.6751 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.0859 -0.2004 -1.5135 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1436 2.2872 -0.1625 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9803 0.3453 2.6308 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5198 0.8841 2.7562 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7779 0.1992 2.5103 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5093 2.4100 -1.2234 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2749 3.0316 0.3425 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3235 2.3343 1.9771 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2679 -1.1974 -0.3680 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5228 -3.2047 -1.1488 H 0 0 0 0 0 0 0 0 0 0 0 0 9.1748 -1.2511 -0.4685 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9496 0.7533 0.3107 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0183 -3.7040 -1.0162 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9776 1.1845 -2.5716 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6571 -0.3050 2.1638 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9358 1.8393 1.8081 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3169 0.8438 0.7686 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1052 0.2417 -1.1722 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5162 -1.2866 1.0815 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4959 -2.7406 -1.4285 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1690 -3.4122 0.1377 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.0044 -2.2030 -0.1501 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.4872 0.7025 -1.6121 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6685 2.8576 0.5016 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3683 -0.1201 3.2571 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 14 17 1 0 4 18 1 0 3 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 24 27 1 0 23 28 1 0 22 29 1 0 21 30 1 0 6 1 1 0 16 11 1 0 27 20 1 0 1 31 1 0 2 32 1 0 5 33 1 0 7 34 1 0 7 35 1 0 12 36 1 0 13 37 1 0 15 38 1 0 16 39 1 0 17 40 1 0 18 41 1 0 20 42 1 1 21 43 1 1 22 44 1 1 23 45 1 6 24 46 1 1 25 47 1 0 25 48 1 0 26 49 1 0 28 50 1 0 29 51 1 0 30 52 1 0 M END

Standard InCHIKey	JAKPEFAGBAKNJU-BFMVXSJESA-N
Standard InCHI	InChI=1S/C20H22O10/c21-8-15-16(24)17(25)18(26)20(30-15)29-14-6-1-10(7-13(14)23)9-28-19(27)11-2-4-12(22)5-3-11/h1-7,15-18,20-26H,8-9H2/t15-,16-,17+,18-,20-/m1/s1
SMILES	c1cc(c(cc1COC(=O)c1ccc(cc1)O)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	422.12	Volume:	398.254 ? Van der Waals volume.
Dense:	1.06	LogP:	1.191 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.597 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.593 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	19.0
TPSA:	166.14 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.338	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.531	Fsp³:	0.35
MCE-18:	67.407 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.402	Fluc inhibitor:	0.437 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.131 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.298 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.25	Promiscuous compounds:	0.346

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.359	MDCK Permeability:	-5.106
Pgp-inhibitor:	0.0	Pgp-substrate:	0.015
PAMPA:	0.989 ? 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):	0.138
20% Bioavailability (F20%):	0.523	30% Bioavailability (F30%):	0.993
50% Bioavailability (F50%):	0.976

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.005	MRP1:	0.251
Plasma Protein Binding (PPB):	83.718%	Volume Distribution (VD):	-0.172
Fu:	16.986% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.036
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.004	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.013
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.311
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.794
HLM stability:	0.034 ? 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):

3.675

Half-life (T1/2):

2.902

ADMET: Toxicity

hERG Blockers:	0.042	hERG Blockers (10um):	0.25
Human Hepatotoxicity (H-HT):	0.082	Drug-induced Liver Injury (DILI):	0.705
AMES Toxicity:	0.609	Rat Oral Acute Toxicity:	0.004
Maximum Recommended Daily Dose:	0.024	Skin Sensitization:	0.99
Carcinogencity:	0.36	Eye Corrosion:	0.0
Eye Irritation:	0.604	Respiratory Toxicity:	0.005
Drug-induced Neurotoxicity:	0.009	Ototoxicity:	0.749
Hematotoxicity:	0.013	Drug-induced Nephrotoxicity:	0.173
Genotoxicity:	0.083	RPMI-8226 Immunitoxicity:	0.085
A549 Cytotoxicity:	0.125	Hek293 Cytotoxicity:	0.463
BCF:	0.571 ? 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:	3.416 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.563 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.039 ? 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
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	Roots	n.a.	n.a.	PMID[22916954]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO28586	Pyrus calleryana	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO28586	Pyrus calleryana	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO28586	Pyrus calleryana	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO8101	Rehmannia glutinosa	Species	Orobanchaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO28586	Pyrus calleryana	Species	Rosaceae	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 NPC258342 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	18550
0.1-0.2	26164
0.2-0.3	4047
0.3-0.4	805
0.4-0.5	248
0.5-0.6	38
0.6-0.7	4
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8413	Intermediate Similarity	NPC191046
0.6301	Remote Similarity	NPC232228
0.6286	Remote Similarity	NPC92054
0.6267	Remote Similarity	NPC194095
0.6	Remote Similarity	NPC481303
0.5846	Remote Similarity	NPC19470
0.5775	Remote Similarity	NPC302989
0.5738	Remote Similarity	NPC9248
0.5735	Remote Similarity	NPC59324
0.5652	Remote Similarity	NPC100389
0.5538	Remote Similarity	NPC310661
0.5529	Remote Similarity	NPC133984
0.55	Remote Similarity	NPC142319
0.5493	Remote Similarity	NPC202700
0.5441	Remote Similarity	NPC105827
0.5397	Remote Similarity	NPC609376
0.5373	Remote Similarity	NPC205054
0.5342	Remote Similarity	NPC106944
0.5333	Remote Similarity	NPC186406
0.5333	Remote Similarity	NPC299435
0.5294	Remote Similarity	NPC214910
0.5294	Remote Similarity	NPC210015
0.5286	Remote Similarity	NPC85799
0.5286	Remote Similarity	NPC303422
0.5278	Remote Similarity	NPC186418
0.5256	Remote Similarity	NPC160882
0.5256	Remote Similarity	NPC145319
0.5231	Remote Similarity	NPC80098
0.5211	Remote Similarity	NPC478871
0.5211	Remote Similarity	NPC478870
0.5211	Remote Similarity	NPC478872
0.5211	Remote Similarity	NPC478873
0.52	Remote Similarity	NPC116229
0.5195	Remote Similarity	NPC217950
0.5195	Remote Similarity	NPC260604
0.5139	Remote Similarity	NPC252169
0.5139	Remote Similarity	NPC469661
0.5139	Remote Similarity	NPC65530
0.5135	Remote Similarity	NPC98777
0.5075	Remote Similarity	NPC40377
0.5065	Remote Similarity	NPC328093
0.5063	Remote Similarity	NPC166180
0.506	Remote Similarity	NPC476866

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC258342 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4677
0.1-0.2	4331
0.2-0.3	132
0.3-0.4	8
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
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
		NPD

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