NPASS Compound

Natural Product: NPC203467

Natural Product ID	NPC203467
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	KJXSIXMJHKAJOD-CABCVRRESA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	12306070
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0000337] Flavans [CHEMONTID:0003012] Flavan-3-ols [CHEMONTID:0001584] Catechins [CHEMONTID:0001594] Epigallocatechins

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 35 37 0 0 0 0 0 0 0 0999 V2000 2.0146 0.5541 -0.8110 C 0 0 0 0 0 0 0 0 0 0 0 0 1.4069 0.6778 0.4121 C 0 0 0 0 0 0 0 0 0 0 0 0 1.8297 -0.0945 1.5073 C 0 0 0 0 0 0 0 0 0 0 0 0 2.8685 -0.9881 1.3515 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4921 -1.1260 0.1277 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0474 -0.3453 -0.9347 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6823 -0.4987 -2.1436 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5421 -2.0154 -0.0687 O 0 0 0 0 0 0 0 0 0 0 0 0 3.3110 -1.7706 2.4242 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3119 1.5884 0.6772 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.3214 2.2800 -0.4733 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1580 1.3317 -1.2913 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2057 1.3599 -2.5301 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.9300 0.3543 -0.5617 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9433 -0.3961 -1.1378 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.6766 -1.3281 -0.4343 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.4063 -1.5380 0.9005 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4051 -0.8044 1.4925 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6716 0.1373 0.7615 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6759 0.8534 1.3894 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1260 -2.4768 1.6606 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1921 -0.1595 -2.4918 O 0 0 0 0 0 0 0 0 0 0 0 0 0.4710 3.1044 -1.2143 O 0 0 0 0 0 0 0 0 0 0 0 0 1.6466 1.1696 -1.6128 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3654 -0.0137 2.4803 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2994 0.2004 -2.5628 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5112 -1.7922 0.1076 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0616 -2.7516 2.3870 H 0 0 0 0 0 0 0 0 0 0 0 0 0.6701 2.3734 1.3957 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1071 2.9615 -0.0157 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4599 -1.9010 -0.9007 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1914 -0.9736 2.5573 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1174 -2.3106 1.8896 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9397 0.5063 -2.6896 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0042 3.8318 -1.6478 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 5 8 1 0 4 9 1 0 2 10 1 0 10 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 2 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 17 21 1 0 15 22 1 0 11 23 1 0 6 1 1 0 20 10 1 0 19 14 1 0 1 24 1 0 3 25 1 0 7 26 1 0 8 27 1 0 9 28 1 0 10 29 1 1 11 30 1 1 16 31 1 0 18 32 1 0 21 33 1 0 22 34 1 0 23 35 1 0 M END

Standard InCHIKey	KJXSIXMJHKAJOD-CABCVRRESA-N
Standard InCHI	InChI=1S/C15H12O8/c16-6-3-7(17)11-10(4-6)23-15(14(22)13(11)21)5-1-8(18)12(20)9(19)2-5/h1-4,14-20,22H/t14-,15-/m0/s1
SMILES	c1c(cc(c(c1O)O)O)[C@H]1[C@H](C(=O)c2c(cc(cc2O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	320.05	Volume:	294.193 ? Van der Waals volume.
Dense:	1.088	LogP:	0.465 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.797 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.853 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	18.0
TPSA:	147.68 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	6.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.424	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.534	Fsp³:	0.133
MCE-18:	64.706 ? 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:	Rejected	BMS Rule:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.813	Fluc inhibitor:	0.381 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.147 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.165 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.612	Promiscuous compounds:	0.593

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.445	MDCK Permeability:	-4.965
Pgp-inhibitor:	0.012	Pgp-substrate:	0.077
PAMPA:	0.89 ? 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):	0.08
20% Bioavailability (F20%):	0.544	30% Bioavailability (F30%):	0.997
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.846
Plasma Protein Binding (PPB):	91.668%	Volume Distribution (VD):	-0.248
Fu:	8.829% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.985
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.851
BSEP inhibitor:	0.018

ADMET: Metabolism

CYP1A2-inhibitor:	0.869	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.024
CYP2C9-inhibitor:	0.007	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.016	CYP2D6-substrate:	0.986
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.925
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.942
HLM stability:	0.251 ? 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):

9.316

Half-life (T1/2):

2.014

ADMET: Toxicity

hERG Blockers:	0.042	hERG Blockers (10um):	0.758
Human Hepatotoxicity (H-HT):	0.638	Drug-induced Liver Injury (DILI):	0.645
AMES Toxicity:	0.871	Rat Oral Acute Toxicity:	0.516
Maximum Recommended Daily Dose:	0.816	Skin Sensitization:	0.997
Carcinogencity:	0.26	Eye Corrosion:	0.022
Eye Irritation:	0.997	Respiratory Toxicity:	0.698
Drug-induced Neurotoxicity:	0.003	Ototoxicity:	0.892
Hematotoxicity:	0.041	Drug-induced Nephrotoxicity:	0.057
Genotoxicity:	0.998	RPMI-8226 Immunitoxicity:	0.015
A549 Cytotoxicity:	0.923	Hek293 Cytotoxicity:	0.532
BCF:	0.797 ? 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:	3.381 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.381 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.786 ? 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
NPO21072	Rhododendron dauricum	Species	Ericaceae	Eukaryota	n.a.	whole plant	n.a.	DOI[10.1007/BF02329610]
NPO21072	Rhododendron dauricum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[15270561]
NPO21072	Rhododendron dauricum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO21072	Rhododendron dauricum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO21072	Rhododendron dauricum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21072	Rhododendron dauricum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO21072	Rhododendron dauricum	Species	Ericaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO21072	Rhododendron dauricum	Species	Ericaceae	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 NPC203467 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	26805
0.1-0.2	19983
0.2-0.3	2555
0.3-0.4	335
0.4-0.5	116
0.5-0.6	27
0.6-0.7	15
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC19721
0.8261	Intermediate Similarity	NPC21835
0.7959	Intermediate Similarity	NPC36835
0.7959	Intermediate Similarity	NPC246162
0.7959	Intermediate Similarity	NPC9743
0.7959	Intermediate Similarity	NPC260491
0.7959	Intermediate Similarity	NPC61506
0.7959	Intermediate Similarity	NPC240476
0.76	Intermediate Similarity	NPC250922
0.7347	Intermediate Similarity	NPC62290
0.7347	Intermediate Similarity	NPC142731
0.7347	Intermediate Similarity	NPC326506
0.7347	Intermediate Similarity	NPC4152
0.7059	Intermediate Similarity	NPC44721
0.7059	Intermediate Similarity	NPC211466
0.7059	Intermediate Similarity	NPC605332
0.6981	Remote Similarity	NPC320825
0.6863	Remote Similarity	NPC325028
0.6863	Remote Similarity	NPC256346
0.6863	Remote Similarity	NPC606550
0.6731	Remote Similarity	NPC606962
0.6667	Remote Similarity	NPC279417
0.6667	Remote Similarity	NPC208176
0.6667	Remote Similarity	NPC49130
0.6429	Remote Similarity	NPC326037
0.6429	Remote Similarity	NPC13858
0.6415	Remote Similarity	NPC306607
0.6275	Remote Similarity	NPC268266
0.6275	Remote Similarity	NPC42760
0.6275	Remote Similarity	NPC220825
0.6275	Remote Similarity	NPC268342
0.5636	Remote Similarity	NPC246328
0.5636	Remote Similarity	NPC27532
0.5636	Remote Similarity	NPC201837
0.5614	Remote Similarity	NPC611035
0.5441	Remote Similarity	NPC186847
0.5303	Remote Similarity	NPC63438
0.5286	Remote Similarity	NPC36916
0.5286	Remote Similarity	NPC36
0.5286	Remote Similarity	NPC7154
0.5286	Remote Similarity	NPC125039
0.5286	Remote Similarity	NPC7688
0.5263	Remote Similarity	NPC176869
0.5263	Remote Similarity	NPC321011
0.5263	Remote Similarity	NPC294852
0.5263	Remote Similarity	NPC3779
0.5263	Remote Similarity	NPC188679
0.5211	Remote Similarity	NPC138688
0.5211	Remote Similarity	NPC72787
0.5211	Remote Similarity	NPC217795
0.5211	Remote Similarity	NPC58223
0.5185	Remote Similarity	NPC1940
0.5172	Remote Similarity	NPC609065
0.5139	Remote Similarity	NPC279209
0.5139	Remote Similarity	NPC102277
0.5139	Remote Similarity	NPC479117
0.5091	Remote Similarity	NPC182421
0.5088	Remote Similarity	NPC122828

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC203467 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5801
0.1-0.2	3312
0.2-0.3	26
0.3-0.4	2
0.4-0.5	6
0.5-0.6	3
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
0.5286	Remote Similarity	NPD6166	Phase 2
0.5286	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.5286	Remote Similarity	NPD6168	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