NPASS Compound

Natural Product: NPC555744

Natural Product ID	NPC555744
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	2-(3,4-dihydroxyphenyl)-5,6-dihydroxy-7-[(2~{R},3~{S},4~{S},5~{S})-3,4,5-trihydroxytetrahydropyran-2-yl]oxy-chromen-4-one
IUPAC Name	2-(3,4-dihydroxyphenyl)-5,6-dihydroxy-7-[(2~{R},3~{S},4~{S},5~{S})-3,4,5-trihydroxytetrahydropyran-2-yl]oxy-chromen-4-one
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 49 52 0 0 0 0 0 0 0 0999 V2000 2.9313 -4.0277 -0.3608 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6077 -2.8424 -0.2530 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5121 -1.8086 -0.0955 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0451 -0.5243 0.0150 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9806 0.5906 0.1828 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4906 1.8957 0.2943 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3100 2.9736 0.4519 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6651 2.7915 0.5051 C 0 0 0 0 0 0 0 0 0 0 0 0 6.5192 3.8700 0.6647 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1867 1.5349 0.4004 C 0 0 0 0 0 0 0 0 0 0 0 0 7.5574 1.2757 0.4462 O 0 0 0 0 0 0 0 0 0 0 0 0 5.3240 0.4370 0.2383 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7345 -0.2653 -0.0278 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8465 -1.1993 -0.1739 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5223 -0.8956 -0.2151 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4888 -1.8440 -0.3669 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8110 -1.5502 -0.4067 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4447 -0.3184 -0.3106 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1887 0.0119 -1.4352 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7442 1.2559 -1.3999 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5285 1.5428 -0.1433 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.0847 2.7937 -0.1219 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6711 1.2517 1.0701 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.4377 1.9320 0.9649 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.3154 -0.2344 0.9563 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.5738 -0.6522 2.0387 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.0478 -3.1675 -0.4830 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0262 -4.1294 -0.6369 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2877 -3.4794 -0.4445 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7195 -4.8022 -0.5610 O 0 0 0 0 0 0 0 0 0 0 0 0 1.2535 -2.5026 -0.2897 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5752 -2.0708 -0.0663 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4261 2.0174 0.2503 H 0 0 0 0 0 0 0 0 0 0 0 0 3.9316 3.9763 0.5376 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2056 4.1338 -0.0395 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9184 0.4971 0.9870 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7696 -0.5569 0.1572 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.7902 0.1713 -0.1168 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7213 0.5064 -0.1847 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9076 2.0045 -1.4219 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3355 1.4525 -2.3153 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3704 0.8033 -0.1187 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4402 3.5304 -0.1640 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1740 1.4746 2.0101 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5539 2.8366 0.5979 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2586 -0.7880 0.8272 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9550 -0.3941 2.8954 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5644 -4.3762 0.1773 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1575 -5.1315 -1.4162 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 2 0 8 9 1 0 8 10 1 0 10 11 1 0 10 12 2 0 4 13 1 0 13 14 1 0 14 15 2 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 16 27 2 0 27 28 1 0 27 29 1 0 29 30 1 0 29 31 2 0 31 2 1 0 12 5 1 0 31 14 1 0 25 18 1 0 3 32 1 0 6 33 1 0 7 34 1 0 9 35 1 0 11 36 1 0 12 37 1 0 15 38 1 0 18 39 1 1 20 40 1 0 20 41 1 0 21 42 1 1 22 43 1 0 23 44 1 1 24 45 1 0 25 46 1 6 26 47 1 0 28 48 1 0 30 49 1 0 M END

Standard InCHIKey	MWTIXVAPAPFDDA-XABUNACWSA-N
Standard InCHI	InChI=1S/C20H18O11/c21-8-2-1-7(3-9(8)22)12-4-10(23)15-13(30-12)5-14(17(26)18(15)27)31-20-19(28)16(25)11(24)6-29-20/h1-5,11,16,19-22,24-28H,6H2/t11-,16-,19-,20+/m0/s1
SMILES	O=C1C=C(C2=CC=C(O)C(O)=C2)OC2=CC(O[C@H]3OC[C@H](O)[C@H](O)[C@@H]3O)=C(O)C(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	434.08	Volume:	395.851 ? Van der Waals volume.
Dense:	1.097	LogP:	0.875 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.052 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.215 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	24.0
TPSA:	190.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	7.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.277	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.971	Fsp³:	0.25
MCE-18:	88.4 ? 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:	0.631	Fluc inhibitor:	0.326 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.976 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.83 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.115	Promiscuous compounds:	0.882

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.247	MDCK Permeability:	-4.934
Pgp-inhibitor:	0.0	Pgp-substrate:	0.553
PAMPA:	0.999 ? 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):	0.417
20% Bioavailability (F20%):	0.995	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.814
Plasma Protein Binding (PPB):	81.189%	Volume Distribution (VD):	-0.013
Fu:	17.06% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.971
OATP1B3 inhibitor:	0.986	BCRP inhibitor:	0.971
BSEP inhibitor:	0.003

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.015	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.093
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.783
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.692
HLM stability:	0.103 ? 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):

3.048

Half-life (T1/2):

3.524

ADMET: Toxicity

hERG Blockers:	0.017	hERG Blockers (10um):	0.305
Human Hepatotoxicity (H-HT):	0.604	Drug-induced Liver Injury (DILI):	0.962
AMES Toxicity:	0.879	Rat Oral Acute Toxicity:	0.292
Maximum Recommended Daily Dose:	0.232	Skin Sensitization:	0.999
Carcinogencity:	0.215	Eye Corrosion:	0.009
Eye Irritation:	0.987	Respiratory Toxicity:	0.325
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.547
Hematotoxicity:	0.217	Drug-induced Nephrotoxicity:	0.282
Genotoxicity:	0.983	RPMI-8226 Immunitoxicity:	0.095
A549 Cytotoxicity:	0.976	Hek293 Cytotoxicity:	0.46
BCF:	0.727 ? 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:	3.306 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.743 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.235 ? 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
NPO30681	Lippia nodiflora	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO30681	Lippia nodiflora	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO30681	Lippia nodiflora	Species	Verbenaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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 NPC555744 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	23367
0.1-0.2	23769
0.2-0.3	1881
0.3-0.4	649
0.4-0.5	153
0.5-0.6	28
0.6-0.7	6
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	Natural Product ID
0.7534	Intermediate Similarity	NPC58716
0.6769	Remote Similarity	NPC162313
0.6494	Remote Similarity	NPC146792
0.6429	Remote Similarity	NPC3583
0.6375	Remote Similarity	NPC43211
0.6154	Remote Similarity	NPC45618
0.6049	Remote Similarity	NPC237435
0.5802	Remote Similarity	NPC245014
0.5783	Remote Similarity	NPC115760
0.575	Remote Similarity	NPC19709
0.5679	Remote Similarity	NPC189142
0.5679	Remote Similarity	NPC77660
0.5652	Remote Similarity	NPC198826
0.5647	Remote Similarity	NPC190003
0.561	Remote Similarity	NPC45638
0.557	Remote Similarity	NPC276222
0.557	Remote Similarity	NPC274618
0.557	Remote Similarity	NPC118284
0.557	Remote Similarity	NPC608147
0.5542	Remote Similarity	NPC201292
0.5517	Remote Similarity	NPC254540
0.5493	Remote Similarity	NPC212678
0.5476	Remote Similarity	NPC20505
0.5333	Remote Similarity	NPC210073
0.5326	Remote Similarity	NPC65711
0.5286	Remote Similarity	NPC275722
0.5211	Remote Similarity	NPC57030
0.5139	Remote Similarity	NPC108406
0.5139	Remote Similarity	NPC25270
0.5119	Remote Similarity	NPC168822
0.5106	Remote Similarity	NPC229409
0.5062	Remote Similarity	NPC54802
0.5062	Remote Similarity	NPC197304
0.5059	Remote Similarity	NPC84265
0.5056	Remote Similarity	NPC477848

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC555744 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5464
0.1-0.2	3626
0.2-0.3	47
0.3-0.4	9
0.4-0.5	3
0.5-0.6	0
0.6-0.7	1
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
0.6049	Remote 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