NPASS Compound

Natural Product: NPC251656

Natural Product ID	NPC251656
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	FBPFZTCFMRRESA-ZXXMMSQZSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	90540
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0004603] Organic oxygen compounds [CHEMONTID:0000323] Organooxygen compounds [CHEMONTID:0000011] Carbohydrates and carbohydrate conjugates [CHEMONTID:0002210] Sugar alcohols

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 26 25 0 0 0 0 0 0 0 0999 V2000 2.9805 -0.1560 0.0550 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6671 -0.8825 -0.1166 C 0 0 2 0 0 0 0 0 0 0 0 0 0.4892 0.0622 -0.0182 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.7742 -0.7326 -0.0899 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.0053 0.1003 0.1198 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.1085 1.2285 -0.8794 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2111 2.0072 -0.5695 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1280 -0.7041 0.1050 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.7370 -1.6651 0.9741 O 0 0 0 0 0 0 0 0 0 0 0 0 0.5049 0.7015 1.2376 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6047 -1.8523 0.8859 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1394 0.8442 -0.9101 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0769 0.3018 1.0602 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7906 -0.8946 -0.0662 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6734 -1.3414 -1.1121 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5361 0.7689 -0.8511 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8239 -1.3427 -1.0136 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9240 0.5561 1.1371 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1844 0.8888 -1.9095 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2137 1.8657 -0.7532 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6565 1.7296 0.2817 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4455 -0.8711 -0.8193 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9529 -1.1525 1.8096 H 0 0 0 0 0 0 0 0 0 0 0 0 0.9147 1.5877 1.1001 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1090 -2.6523 0.5928 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6784 1.6044 -0.5527 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 5 8 1 0 4 9 1 0 3 10 1 0 2 11 1 0 1 12 1 0 1 13 1 0 1 14 1 0 2 15 1 6 3 16 1 6 4 17 1 6 5 18 1 1 6 19 1 0 6 20 1 0 7 21 1 0 8 22 1 0 9 23 1 0 10 24 1 0 11 25 1 0 12 26 1 0 M END

Standard InCHIKey	FBPFZTCFMRRESA-ZXXMMSQZSA-N
Standard InCHI	InChI=1S/C6H14O6/c7-1-3(9)5(11)6(12)4(10)2-8/h3-12H,1-2H2/t3-,4-,5+,6+/m1/s1
SMILES	C([C@H]([C@@H]([C@H]([C@@H](CO)O)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	182.08	Volume:	165.074 ? Van der Waals volume.
Dense:	1.103	LogP:	-1.864 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-1.731 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	0.347 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	0.0
TPSA:	121.38 ? Topological Polar Surface Area.	H-Bond Acceptor:	6.0
H-Bond Donor:	6.0	Rings:	0.0
Heavy Atoms:	6.0

MedChem Properties

QED Drug-Likeness Score:	0.261	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.558	Fsp³:	1.0
MCE-18:	4.0 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.012	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.023 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.0 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.57	Promiscuous compounds:	0.038

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.766	MDCK Permeability:	-4.405
Pgp-inhibitor:	0.0	Pgp-substrate:	0.098
PAMPA:	0.998 ? 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):	0.554
20% Bioavailability (F20%):	0.087	30% Bioavailability (F30%):	0.508
50% Bioavailability (F50%):	0.667

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.614	MRP1:	0.009
Plasma Protein Binding (PPB):	27.786%	Volume Distribution (VD):	-0.477
Fu:	80.106% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.993
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.063
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.069
CYP2C9-inhibitor:	0.883	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.0
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.013
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.792
HLM stability:	0.003 ? 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):

2.931

Half-life (T1/2):

1.817

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.041
Human Hepatotoxicity (H-HT):	0.341	Drug-induced Liver Injury (DILI):	0.011
AMES Toxicity:	0.65	Rat Oral Acute Toxicity:	0.004
Maximum Recommended Daily Dose:	0.002	Skin Sensitization:	0.945
Carcinogencity:	0.182	Eye Corrosion:	0.001
Eye Irritation:	0.685	Respiratory Toxicity:	0.001
Drug-induced Neurotoxicity:	0.003	Ototoxicity:	0.979
Hematotoxicity:	0.073	Drug-induced Nephrotoxicity:	0.539
Genotoxicity:	0.002	RPMI-8226 Immunitoxicity:	0.052
A549 Cytotoxicity:	0.037	Hek293 Cytotoxicity:	0.017
BCF:	0.099 ? 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:	1.068 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	1.814 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	1.17 ? 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
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	fruit	n.a.	DOI[10.1007/s11306-014-0728-9]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	DOI[10.1038/sdata.2014.29]
NPO19009	Ipomoea orizabensis	Species	Convolvulaceae	Eukaryota	Roots	Mexican	n.a.	PMID[10479311]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	fruit	n.a.	PMID[11171227]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	fruit	n.a.	PMID[12576668]
NPO19009	Ipomoea orizabensis	Species	Convolvulaceae	Eukaryota	crude resin	Mexican	n.a.	PMID[16562846]
NPO14026.1	Vitex negundo var. cannabifolia	Varieties	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[25245917]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	seed	n.a.	PMID[25891114]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[8987503]
NPO18614	Gentiana turkestanorum	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21485	Polygala sibirica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14026.1	Vitex negundo var. cannabifolia	Varieties	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20669	Baccharis rhetinodes	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19772	Ceroplastes ceriferus	Species	Coccidae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21549	Consolida raveyi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4243	Didymocarpus leucocalyx	Species	Gesneriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19009	Ipomoea orizabensis	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO16442	Omphalia campanella	n.a.	n.a.	n.a.	n.a.	n.a.	n.a.	Database[COCONUT]
NPO14033	Torilis arvensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20473	Vaccinium membranaceum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21485	Polygala sibirica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	fruit	n.a.	Database[MetaboLights]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[MetaboLights]
NPO18614	Gentiana turkestanorum	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21485	Polygala sibirica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21485	Polygala sibirica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21485	Polygala sibirica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO21485	Polygala sibirica	Species	Polygalaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19772	Ceroplastes ceriferus	Species	Coccidae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO19009	Ipomoea orizabensis	Species	Convolvulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO18614	Gentiana turkestanorum	Species	Gentianaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21080	Solanum lycopersicum	Species	Solanaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20669	Baccharis rhetinodes	Species	Asteraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO21549	Consolida raveyi	Species	Ranunculaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14033	Torilis arvensis	Species	Apiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO4243	Didymocarpus leucocalyx	Species	Gesneriaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO14026.1	Vitex negundo var. cannabifolia	Varieties	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20473	Vaccinium membranaceum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16442	Omphalia campanella	n.a.	n.a.	n.a.	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 NPC251656 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	45619
0.1-0.2	3963
0.2-0.3	228
0.3-0.4	19
0.4-0.5	10
0.5-0.6	5
0.6-0.7	3
0.7-0.8	0
0.8-0.85	5
0.85-0.9	0
0.9-0.95	1
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC293908
1.0	High Similarity	NPC66052
1.0	High Similarity	NPC192065
1.0	High Similarity	NPC86412
0.9091	High Similarity	NPC31981
0.8182	Intermediate Similarity	NPC197207
0.8182	Intermediate Similarity	NPC187058
0.8182	Intermediate Similarity	NPC182541
0.8182	Intermediate Similarity	NPC127074
0.8182	Intermediate Similarity	NPC149070
0.6364	Remote Similarity	NPC301586
0.6364	Remote Similarity	NPC317060
0.6364	Remote Similarity	NPC33415
0.5882	Remote Similarity	NPC606151
0.5455	Remote Similarity	NPC157340
0.5455	Remote Similarity	NPC114270
0.5294	Remote Similarity	NPC270088
0.5294	Remote Similarity	NPC200137

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC251656 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	8672
0.1-0.2	387
0.2-0.3	59
0.3-0.4	6
0.4-0.5	14
0.5-0.6	5
0.6-0.7	1
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	3

Similarity Score	Similarity Level	Drug ID	Developmental Stage
1.0	High Similarity	NPD9051	Approved
1.0	High Similarity	NPD9052	Phase 4
1.0	High Similarity	NPD9053	Phase 4
0.8182	Intermediate Similarity	NPD8814	Phase 3
0.6364	Remote Similarity	NPD8549	Clinical (unspecified phase)
0.5882	Remote Similarity	NPD9001	Phase 2
0.5882	Remote Similarity	NPD9002	Approved
0.5455	Remote Similarity	NPD8225	Phase 3
0.5455	Remote Similarity	NPD8226	Phase 4
0.5455	Remote Similarity	NPD8231	Phase 4

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