NPASS Compound

Natural Product: NPC501977

Natural Product ID	NPC501977
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2S,3S,4S,5R,6S)-6-{[2-(3,4-dihydroxyphenyl)-5,6-dihydroxy-4-oxo-4H-chromen-7-yl]oxy}-3,4,5-trihydroxyoxane-2-carboxylic acid
IUPAC Name	(2~{S},3~{S},4~{S},5~{R},6~{S})-6-[2-(3,4-dihydroxyphenyl)-5,6-dihydroxy-4-oxo-chromen-7-yl]oxy-3,4,5-trihydroxy-tetrahydropyran-2-carboxylic acid
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds]

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 55 0 0 0 0 0 0 0 0999 V2000 -4.0084 0.6593 -3.2823 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.6543 -0.0511 -2.3087 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3122 -0.3521 -2.1821 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7205 -0.5023 -1.3807 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.3089 -1.2593 -0.3489 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7170 -0.6039 0.7191 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4149 -0.3447 0.4486 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2061 -0.7095 0.9125 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0772 -0.1554 0.2890 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2047 -0.4562 0.6794 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3510 -1.3392 1.7263 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2526 -1.8900 2.3468 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4723 -2.7737 3.3966 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0115 -1.5818 1.9482 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0703 -2.1817 2.6277 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6411 -1.6543 2.1338 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7676 -2.4509 3.0782 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6834 -1.0613 1.4619 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4827 -0.1839 0.4201 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6091 0.4491 -0.2968 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3245 1.3156 -1.3274 C 0 0 0 0 0 0 0 0 0 0 0 0 5.3255 1.9491 -2.0486 C 0 0 0 0 0 0 0 0 0 0 0 0 6.6543 1.7232 -1.7462 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6758 2.3522 -2.4614 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9510 0.8577 -0.7164 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2854 0.6338 -0.4162 O 0 0 0 0 0 0 0 0 0 0 0 0 5.9261 0.2236 0.0048 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2486 0.0814 0.0730 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5221 0.6065 1.1610 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.7380 0.1383 1.6535 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8208 1.5250 -0.0030 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7112 2.1683 -0.4914 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.5485 0.7051 -1.0277 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.7688 0.3260 -0.4729 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.6504 0.0730 -2.8185 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4001 -1.1504 -2.0146 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.8211 -1.3165 1.5586 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2038 0.5458 -0.5427 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4019 -2.3659 4.3321 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.9863 -3.1910 2.8084 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6902 -1.3081 1.7809 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2751 1.4973 -1.5701 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0898 2.6307 -2.8596 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5306 1.8975 -2.7203 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5796 -0.0992 0.2169 H 0 0 0 0 0 0 0 0 0 0 0 0 6.1905 -0.4467 0.8033 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9598 1.1725 1.9007 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6390 -0.6824 2.1975 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5474 2.2877 0.3800 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8830 1.8892 -0.0684 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7012 1.2910 -1.9593 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2105 1.1128 -0.0690 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 12 14 2 0 14 15 1 0 11 16 1 0 16 17 2 0 16 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 23 24 1 0 23 25 1 0 25 26 1 0 25 27 2 0 19 28 1 0 6 29 1 0 29 30 1 0 29 31 1 0 31 32 1 0 31 33 1 0 33 34 1 0 33 4 1 0 14 8 1 0 27 20 1 0 28 10 1 0 3 35 1 0 4 36 1 6 6 37 1 1 9 38 1 0 13 39 1 0 15 40 1 0 18 41 1 0 21 42 1 0 22 43 1 0 24 44 1 0 26 45 1 0 27 46 1 0 29 47 1 1 30 48 1 0 31 49 1 1 32 50 1 0 33 51 1 6 34 52 1 0 M END

Standard InCHIKey	OEMKKZWJXLXULA-ZFORQUDYSA-N
Standard InCHI	InChI=1S/C21H18O13/c22-7-2-1-6(3-8(7)23)10-4-9(24)13-11(32-10)5-12(14(25)15(13)26)33-21-18(29)16(27)17(28)19(34-21)20(30)31/h1-5,16-19,21-23,25-29H,(H,30,31)/t16-,17-,18+,19-,21+/m0/s1
SMILES	O=C(O)[C@H]1O[C@@H](OC2=CC3=C(C(O)=C2O)C(=O)C=C(C2=CC=C(O)C(O)=C2)O3)[C@H](O)[C@@H](O)[C@@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	478.07	Volume:	428.091 ? Van der Waals volume.
Dense:	1.117	LogP:	0.584 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.964 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.778 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	25.0
TPSA:	227.58 ? Topological Polar Surface Area.	H-Bond Acceptor:	13.0
H-Bond Donor:	8.0	Rings:	4.0
Heavy Atoms:	13.0

MedChem Properties

QED Drug-Likeness Score:	0.223	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.11	Fsp³:	0.238
MCE-18:	94.769 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.474	Fluc inhibitor:	0.319 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.969 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.871 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.321	Promiscuous compounds:	0.553

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.807	MDCK Permeability:	-5.021
Pgp-inhibitor:	0.0	Pgp-substrate:	0.189
PAMPA:	1.0 ? 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):	0.108
20% Bioavailability (F20%):	0.862	30% Bioavailability (F30%):	0.974
50% Bioavailability (F50%):	0.994

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.968
Plasma Protein Binding (PPB):	81.338%	Volume Distribution (VD):	0.012
Fu:	14.476% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.046
OATP1B3 inhibitor:	0.146	BCRP inhibitor:	0.264
BSEP inhibitor:	0.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.001
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.008
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.298
HLM stability:	0.004 ? 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):

2.004

Half-life (T1/2):

4.137

ADMET: Toxicity

hERG Blockers:	0.006	hERG Blockers (10um):	0.069
Human Hepatotoxicity (H-HT):	0.335	Drug-induced Liver Injury (DILI):	0.941
AMES Toxicity:	0.526	Rat Oral Acute Toxicity:	0.091
Maximum Recommended Daily Dose:	0.122	Skin Sensitization:	0.996
Carcinogencity:	0.028	Eye Corrosion:	0.0
Eye Irritation:	0.889	Respiratory Toxicity:	0.05
Drug-induced Neurotoxicity:	0.001	Ototoxicity:	0.739
Hematotoxicity:	0.051	Drug-induced Nephrotoxicity:	0.287
Genotoxicity:	0.891	RPMI-8226 Immunitoxicity:	0.059
A549 Cytotoxicity:	0.487	Hek293 Cytotoxicity:	0.106
BCF:	0.22 ? 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:	2.75 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.156 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.476 ? 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
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[10096857]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23507152]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33321838]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36432812]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36840093]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[36987013]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37176852]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37751472]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37836118]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[37836125]
NPO9627	Plantago maritima	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	Stem	n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.		Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	Shoot	n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	Leaf Essent. Oil	n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO6098	Salvia officinalis	Species	Lamiaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO9627	Plantago maritima	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO6098	Salvia officinalis	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 NPC501977 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	26431
0.1-0.2	21213
0.2-0.3	1590
0.3-0.4	527
0.4-0.5	65
0.5-0.6	19
0.6-0.7	7
0.7-0.8	0
0.8-0.85	1
0.85-0.9	2
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8904	High Similarity	NPC43211
0.8514	High Similarity	NPC237435
0.8158	Intermediate Similarity	NPC115760
0.7792	Intermediate Similarity	NPC20505
0.6914	Remote Similarity	NPC135277
0.6914	Remote Similarity	NPC282169
0.6875	Remote Similarity	NPC58716
0.6588	Remote Similarity	NPC600989
0.6429	Remote Similarity	NPC608742
0.6338	Remote Similarity	NPC162313
0.6118	Remote Similarity	NPC210094
0.5952	Remote Similarity	NPC146792
0.5934	Remote Similarity	NPC3583
0.593	Remote Similarity	NPC235260
0.593	Remote Similarity	NPC155763
0.5814	Remote Similarity	NPC101191
0.5773	Remote Similarity	NPC253685
0.5747	Remote Similarity	NPC49344
0.5647	Remote Similarity	NPC45618
0.5361	Remote Similarity	NPC229409
0.5341	Remote Similarity	NPC245014
0.5333	Remote Similarity	NPC198826
0.5287	Remote Similarity	NPC19709
0.5281	Remote Similarity	NPC138927
0.5269	Remote Similarity	NPC107987
0.5227	Remote Similarity	NPC189142
0.5227	Remote Similarity	NPC77660
0.5195	Remote Similarity	NPC212678
0.5169	Remote Similarity	NPC45638
0.5111	Remote Similarity	NPC201292

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC501977 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4788
0.1-0.2	4298
0.2-0.3	55
0.3-0.4	7
0.4-0.5	1
0.5-0.6	0
0.6-0.7	0
0.7-0.8	0
0.8-0.85	0
0.85-0.9	1
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.8514	High Similarity	NPD4338	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