NPASS Compound

Natural Product: NPC502109

Natural Product ID	NPC502109
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{R},3~{S})-2-(3,4-dihydroxyphenyl)-6-[4,5-dihydroxy-2-[(2~{R},3~{S})-3,5,7-trihydroxychroman-2-yl]phenyl]chromane-3,5,7-triol
IUPAC Name	(2~{R},3~{S})-2-(3,4-dihydroxyphenyl)-6-[4,5-dihydroxy-2-[(2~{R},3~{S})-3,5,7-trihydroxychroman-2-yl]phenyl]chromane-3,5,7-triol
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 68 73 0 0 0 0 0 0 0 0999 V2000 -2.7893 -4.7629 -1.0521 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.2529 -3.5613 -0.5145 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3725 -3.5238 0.2895 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.8233 -2.3394 0.8150 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.9464 -2.3476 1.6136 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1313 -1.1628 0.5252 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6964 0.0730 1.1412 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5646 1.0822 1.1797 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.0305 2.3043 1.6589 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0826 1.2003 -0.2719 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.4049 2.4526 -0.5285 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1501 3.5636 -0.8888 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5710 4.7952 -1.1489 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3242 5.9090 -1.5106 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.2097 4.9309 -1.0489 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5948 6.1530 -1.3030 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4539 3.8359 -0.6917 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.0646 2.5958 -0.4326 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2416 1.4658 -0.0600 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0273 1.2472 1.2710 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.4844 2.1007 2.2390 O 0 0 0 0 0 0 0 0 0 0 0 0 0.8140 0.1747 1.6907 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3306 -0.6785 0.7680 C 0 0 0 0 0 0 0 0 0 0 0 0 2.1328 -1.7854 1.0904 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0944 -2.2947 0.2148 C 0 0 2 0 0 0 0 0 0 0 0 0 4.3966 -1.6538 0.5545 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5042 -0.2978 0.7917 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6959 0.3119 1.1063 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8489 -0.4270 1.1975 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0668 0.1631 1.5137 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7771 -1.7811 0.9671 C 0 0 0 0 0 0 0 0 0 0 0 0 7.9184 -2.5524 1.0509 O 0 0 0 0 0 0 0 0 0 0 0 0 5.5773 -2.3776 0.6531 C 0 0 0 0 0 0 0 0 0 0 0 0 2.7768 -2.1911 -1.2225 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6373 -3.4701 -1.8123 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6088 -1.3701 -1.5976 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0811 -0.4874 -0.5649 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2887 0.5935 -0.9822 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0236 0.8064 -2.3242 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3663 0.0276 -0.5266 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.0098 -1.1771 -0.2761 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5915 -2.3759 -0.7810 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1507 -5.6269 -0.6690 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8839 -4.4743 0.4897 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8335 -1.9269 1.3134 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0964 -0.1673 2.1272 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.5107 0.4356 0.4616 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7554 0.6492 1.7898 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.9950 2.3579 1.4030 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.0122 1.1766 -0.8862 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.2147 3.4906 -0.9755 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5940 6.6044 -0.8273 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1831 6.4057 -0.6769 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6024 3.9397 -0.6138 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9328 1.7154 3.0808 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0295 -0.0030 2.7402 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2225 -3.3836 0.4768 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5982 0.3013 0.7230 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7684 1.3890 1.2923 H 0 0 0 0 0 0 0 0 0 0 0 0 8.5265 0.8266 0.8946 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7365 -2.3112 1.5895 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5069 -3.4425 0.4694 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6813 -1.7541 -1.7426 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9710 -4.1822 -1.2358 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7595 -2.0383 -1.9282 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8191 -0.7460 -2.5156 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.1621 -0.0167 -2.8946 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7075 -2.3880 -1.4128 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 4 6 2 0 6 7 1 0 7 8 1 0 8 9 1 0 8 10 1 0 10 11 1 0 11 12 2 0 12 13 1 0 13 14 1 0 13 15 2 0 15 16 1 0 15 17 1 0 17 18 2 0 18 19 1 0 19 20 2 0 20 21 1 0 20 22 1 0 22 23 2 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 29 31 1 0 31 32 1 0 31 33 2 0 25 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 37 38 2 0 38 39 1 0 10 40 1 0 40 41 1 0 41 42 2 0 42 2 1 0 41 6 1 0 18 11 1 0 38 19 1 0 37 23 1 0 33 26 1 0 1 43 1 0 3 44 1 0 5 45 1 0 7 46 1 0 7 47 1 0 8 48 1 1 9 49 1 0 10 50 1 6 12 51 1 0 14 52 1 0 16 53 1 0 17 54 1 0 21 55 1 0 22 56 1 0 25 57 1 1 27 58 1 0 28 59 1 0 30 60 1 0 32 61 1 0 33 62 1 0 34 63 1 6 35 64 1 0 36 65 1 0 36 66 1 0 39 67 1 0 42 68 1 0 M END

Standard InCHIKey	RIGUICSQBGRGSL-BAAZAXTHSA-N
Standard InCHI	InChI=1S/C30H26O12/c31-12-4-18(33)15-8-24(39)30(42-25(15)5-12)14-7-21(36)20(35)6-13(14)27-22(37)10-26-16(28(27)40)9-23(38)29(41-26)11-1-2-17(32)19(34)3-11/h1-7,10,23-24,29-40H,8-9H2/t23-,24-,29+,30+/m0/s1
SMILES	OC1=CC(O)=C2C[C@H](O)[C@@H](C3=CC(O)=C(O)C=C3C3=C(O)C=C4O[C@H](C5=CC=C(O)C(O)=C5)[C@@H](O)CC4=C3O)OC2=C1

Calculated Properties

Physi-Chem Properties

Molecular Weight:	578.14	Volume:	549.942 ? Van der Waals volume.
Dense:	1.051	LogP:	1.1 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.231 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.534 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	34.0
TPSA:	220.76 ? Topological Polar Surface Area.	H-Bond Acceptor:	12.0
H-Bond Donor:	10.0	Rings:	6.0
Heavy Atoms:	12.0

MedChem Properties

QED Drug-Likeness Score:	0.159	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.502	Fsp³:	0.2
MCE-18:	126.667 ? 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:	Accepted	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.764	Fluc inhibitor:	0.297 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.924 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.51 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.564	Promiscuous compounds:	0.261

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-7.101	MDCK Permeability:	-4.858
Pgp-inhibitor:	0.0	Pgp-substrate:	0.171
PAMPA:	0.944 ? 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):	0.001
20% Bioavailability (F20%):	0.956	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.972
Plasma Protein Binding (PPB):	92.246%	Volume Distribution (VD):	0.117
Fu:	11.81% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.994
OATP1B3 inhibitor:	0.991	BCRP inhibitor:	0.001
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.007	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.163
CYP3A4-inhibitor:	0.006	CYP3A4-substrate:	0.776
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.097
HLM stability:	0.0 ? 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):

9.386

Half-life (T1/2):

3.9

ADMET: Toxicity

hERG Blockers:	0.137	hERG Blockers (10um):	0.766
Human Hepatotoxicity (H-HT):	0.774	Drug-induced Liver Injury (DILI):	0.319
AMES Toxicity:	0.509	Rat Oral Acute Toxicity:	0.374
Maximum Recommended Daily Dose:	0.976	Skin Sensitization:	0.998
Carcinogencity:	0.067	Eye Corrosion:	0.0
Eye Irritation:	0.741	Respiratory Toxicity:	0.6
Drug-induced Neurotoxicity:	0.006	Ototoxicity:	0.96
Hematotoxicity:	0.011	Drug-induced Nephrotoxicity:	0.129
Genotoxicity:	0.988	RPMI-8226 Immunitoxicity:	0.04
A549 Cytotoxicity:	0.998	Hek293 Cytotoxicity:	0.903
BCF:	1.002 ? 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:	3.503 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.644 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.053 ? 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
NPO11804	Potentilla erecta	Species	Rosaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO11804	Potentilla erecta	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 NPC502109 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	24106
0.1-0.2	22783
0.2-0.3	2686
0.3-0.4	164
0.4-0.5	82
0.5-0.6	29
0.6-0.7	0
0.7-0.8	2
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
0.7119	Intermediate Similarity	NPC261619
0.7119	Intermediate Similarity	NPC61477
0.7119	Intermediate Similarity	NPC78770
0.7119	Intermediate Similarity	NPC219876
0.7119	Intermediate Similarity	NPC126029
0.7119	Intermediate Similarity	NPC15658
0.5968	Remote Similarity	NPC207179
0.5968	Remote Similarity	NPC167571
0.5968	Remote Similarity	NPC278552
0.5811	Remote Similarity	NPC28440
0.5714	Remote Similarity	NPC268266
0.5714	Remote Similarity	NPC42760
0.5714	Remote Similarity	NPC220825
0.5714	Remote Similarity	NPC268342
0.5588	Remote Similarity	NPC171932
0.5405	Remote Similarity	NPC58190
0.5405	Remote Similarity	NPC108811
0.5405	Remote Similarity	NPC170103
0.5405	Remote Similarity	NPC236202
0.5405	Remote Similarity	NPC262911
0.5405	Remote Similarity	NPC202742
0.5362	Remote Similarity	NPC16435
0.5333	Remote Similarity	NPC246202
0.5333	Remote Similarity	NPC224161
0.5333	Remote Similarity	NPC46335
0.5333	Remote Similarity	NPC294558
0.5333	Remote Similarity	NPC18185
0.5333	Remote Similarity	NPC263940
0.5333	Remote Similarity	NPC279406
0.5333	Remote Similarity	NPC486519
0.5077	Remote Similarity	NPC601844
0.5075	Remote Similarity	NPC47398
0.5075	Remote Similarity	NPC234333
0.5075	Remote Similarity	NPC260898
0.5072	Remote Similarity	NPC61946

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC502109 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4821
0.1-0.2	4272
0.2-0.3	49
0.3-0.4	6
0.4-0.5	0
0.5-0.6	0
0.6-0.7	0
0.7-0.8	2
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
0.7119	Intermediate Similarity	NPD1612	Clinical (unspecified phase)
0.7119	Intermediate Similarity	NPD1613	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