NPASS Compound

Natural Product: NPC564926

Natural Product ID	NPC564926
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-(2,4,5-trimethoxyphenyl)chromen-4-one
IUPAC Name	7-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-3-(2,4,5-trimethoxyphenyl)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 61 64 0 0 0 0 0 0 0 0999 V2000 8.7006 -1.6221 0.6609 C 0 0 0 0 0 0 0 0 0 0 0 0 8.0977 -0.3723 0.9186 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7252 -0.2511 0.7483 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9845 -1.3439 0.3347 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6118 -1.2178 0.1655 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8973 -2.3045 -0.2427 O 0 0 0 0 0 0 0 0 0 0 0 0 4.5444 -3.5345 -0.4879 C 0 0 0 0 0 0 0 0 0 0 0 0 3.9578 -0.0312 0.3979 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5242 0.0353 0.2009 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6211 -0.2477 1.2117 C 0 0 0 0 0 0 0 0 0 0 0 0 0.3260 -0.2048 1.0939 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.1968 0.1304 -0.0636 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5713 0.1934 -0.2487 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1872 0.5340 -1.4227 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5471 0.5921 -1.5905 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5034 0.3301 -0.6402 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.3385 -0.7043 -1.0630 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3786 -0.9845 -0.2198 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.7224 -0.9811 -0.9420 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.7619 -1.2681 -0.0581 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4334 -0.2010 1.0473 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.7033 -0.8253 2.0782 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.1133 1.2477 0.9347 C 0 0 2 0 0 0 0 0 0 0 0 0 -7.2109 2.0743 1.1433 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.4316 1.5143 -0.3819 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.6994 2.7084 -0.3431 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.3177 0.8330 -2.4891 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0533 0.7832 -2.3495 C 0 0 0 0 0 0 0 0 0 0 0 0 0.6111 0.4324 -1.1384 C 0 0 0 0 0 0 0 0 0 0 0 0 1.9743 0.3900 -1.0241 C 0 0 0 0 0 0 0 0 0 0 0 0 2.6881 0.6641 -1.9985 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7079 1.0398 0.8069 C 0 0 0 0 0 0 0 0 0 0 0 0 6.0883 0.9488 0.9869 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8623 2.0182 1.3989 O 0 0 0 0 0 0 0 0 0 0 0 0 6.2334 3.2510 1.6477 C 0 0 0 0 0 0 0 0 0 0 0 0 8.3640 -2.3933 1.4022 H 0 0 0 0 0 0 0 0 0 0 0 0 8.4667 -1.9963 -0.3670 H 0 0 0 0 0 0 0 0 0 0 0 0 9.8143 -1.5727 0.7802 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5067 -2.2652 0.1565 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8231 -4.3655 -0.6575 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1904 -3.8560 0.3633 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2419 -3.4605 -1.3620 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1082 -0.5241 2.1644 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1622 -0.0515 0.6238 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1110 0.0389 0.3356 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.2444 -2.0636 0.0952 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.9177 0.0179 -1.3496 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.7441 -1.7778 -1.7214 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2898 -2.0607 -0.3209 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.5042 -0.2673 1.4062 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2363 -1.5969 1.6790 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3498 1.4860 1.7324 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.8827 3.0121 0.9653 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.1757 1.6480 -1.1917 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.3435 3.4432 -0.4924 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7775 1.1041 -3.4255 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7249 1.0131 -3.1692 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2341 1.9848 0.9988 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5701 3.5847 0.8427 H 0 0 0 0 0 0 0 0 0 0 0 0 6.9763 4.0659 1.8124 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6257 3.2263 2.5916 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 2 0 4 5 1 0 5 6 1 0 6 7 1 0 5 8 2 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 16 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 18 21 1 0 21 22 1 0 21 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 14 27 2 0 27 28 1 0 28 29 2 0 29 30 1 0 30 31 2 0 8 32 1 0 32 33 2 0 33 34 1 0 34 35 1 0 33 3 1 0 30 9 1 0 29 12 1 0 25 16 1 0 1 36 1 0 1 37 1 0 1 38 1 0 4 39 1 0 7 40 1 0 7 41 1 0 7 42 1 0 10 43 1 0 13 44 1 0 16 45 1 1 18 46 1 1 19 47 1 0 19 48 1 0 20 49 1 0 21 50 1 1 22 51 1 0 23 52 1 1 24 53 1 0 25 54 1 6 26 55 1 0 27 56 1 0 28 57 1 0 32 58 1 0 35 59 1 0 35 60 1 0 35 61 1 0 M END

Standard InCHIKey	UWRBYNRWXBTIBN-PFKOEMKTSA-N
Standard InCHI	InChI=1S/C24H26O11/c1-30-15-8-18(32-3)17(31-2)7-13(15)14-10-33-16-6-11(4-5-12(16)20(14)26)34-24-23(29)22(28)21(27)19(9-25)35-24/h4-8,10,19,21-25,27-29H,9H2,1-3H3/t19-,21-,22+,23-,24-/m1/s1
SMILES	COC1=CC(OC)=C(C2=COC3=CC(O[C@@H]4O[C@H](CO)[C@@H](O)[C@H](O)[C@H]4O)=CC=C3C2=O)C=C1OC

Calculated Properties

Physi-Chem Properties

Molecular Weight:	490.15	Volume:	465.035 ? Van der Waals volume.
Dense:	1.054	LogP:	0.707 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.2 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.12 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	7.0	Rigid Bonds:	24.0
TPSA:	157.28 ? Topological Polar Surface Area.	H-Bond Acceptor:	11.0
H-Bond Donor:	4.0	Rings:	4.0
Heavy Atoms:	11.0

MedChem Properties

QED Drug-Likeness Score:	0.369	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	3.787	Fsp³:	0.375
MCE-18:	85.879 ? 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:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.532	Fluc inhibitor:	0.279 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.711 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.463 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.112	Promiscuous compounds:	0.354

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.823	MDCK Permeability:	-5.096
Pgp-inhibitor:	0.061	Pgp-substrate:	0.072
PAMPA:	0.246 ? 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):	0.894
20% Bioavailability (F20%):	0.018	30% Bioavailability (F30%):	0.704
50% Bioavailability (F50%):	0.899

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.196
Plasma Protein Binding (PPB):	69.622%	Volume Distribution (VD):	-0.128
Fu:	30.521% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.946
BSEP inhibitor:	0.232

ADMET: Metabolism

CYP1A2-inhibitor:	0.07	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.07	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.011	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.002
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.001
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.295
HLM stability:	0.009 ? 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):

2.941

Half-life (T1/2):

4.172

ADMET: Toxicity

hERG Blockers:	0.062	hERG Blockers (10um):	0.145
Human Hepatotoxicity (H-HT):	0.763	Drug-induced Liver Injury (DILI):	0.983
AMES Toxicity:	0.896	Rat Oral Acute Toxicity:	0.065
Maximum Recommended Daily Dose:	0.09	Skin Sensitization:	0.908
Carcinogencity:	0.539	Eye Corrosion:	0.0
Eye Irritation:	0.131	Respiratory Toxicity:	0.04
Drug-induced Neurotoxicity:	0.041	Ototoxicity:	0.913
Hematotoxicity:	0.503	Drug-induced Nephrotoxicity:	0.787
Genotoxicity:	0.69	RPMI-8226 Immunitoxicity:	0.183
A549 Cytotoxicity:	0.258	Hek293 Cytotoxicity:	0.272
BCF:	0.402 ? 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:	3.189 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.617 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.812 ? 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
NPO23490	Dalbergia monetaria	Species	Fabaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO23490	Dalbergia monetaria	Species	Fabaceae	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 NPC564926 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	20068
0.1-0.2	25992
0.2-0.3	2848
0.3-0.4	753
0.4-0.5	145
0.5-0.6	41
0.6-0.7	6
0.7-0.8	1
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
0.7808	Intermediate Similarity	NPC45165
0.7215	Intermediate Similarity	NPC229729
0.7215	Intermediate Similarity	NPC601607
0.7143	Intermediate Similarity	NPC161749
0.6667	Remote Similarity	NPC135345
0.6618	Remote Similarity	NPC216314
0.6282	Remote Similarity	NPC25547
0.6098	Remote Similarity	NPC105511
0.6098	Remote Similarity	NPC603782
0.6024	Remote Similarity	NPC73511
0.5976	Remote Similarity	NPC211014
0.593	Remote Similarity	NPC607201
0.5904	Remote Similarity	NPC258035
0.5882	Remote Similarity	NPC224462
0.5765	Remote Similarity	NPC100720
0.5765	Remote Similarity	NPC205076
0.5747	Remote Similarity	NPC307518
0.5733	Remote Similarity	NPC153008
0.5698	Remote Similarity	NPC479402
0.5682	Remote Similarity	NPC48773
0.5682	Remote Similarity	NPC479407
0.5529	Remote Similarity	NPC197896
0.5529	Remote Similarity	NPC313163
0.5529	Remote Similarity	NPC234739
0.5521	Remote Similarity	NPC231194
0.5517	Remote Similarity	NPC481043
0.5493	Remote Similarity	NPC182842
0.5474	Remote Similarity	NPC51326
0.5474	Remote Similarity	NPC257714
0.5464	Remote Similarity	NPC235575
0.5402	Remote Similarity	NPC182045
0.5393	Remote Similarity	NPC479406
0.5349	Remote Similarity	NPC156457
0.5325	Remote Similarity	NPC103409
0.5281	Remote Similarity	NPC243930
0.5233	Remote Similarity	NPC58053
0.5222	Remote Similarity	NPC607707
0.5176	Remote Similarity	NPC487214
0.5172	Remote Similarity	NPC168822
0.5169	Remote Similarity	NPC479401
0.5169	Remote Similarity	NPC80140
0.5169	Remote Similarity	NPC609451
0.5135	Remote Similarity	NPC185607
0.5114	Remote Similarity	NPC186807
0.5111	Remote Similarity	NPC43761
0.5065	Remote Similarity	NPC262623
0.5063	Remote Similarity	NPC478213
0.5059	Remote Similarity	NPC607700
0.5057	Remote Similarity	NPC259070
0.5057	Remote Similarity	NPC110349
0.5056	Remote Similarity	NPC138540

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC564926 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4830
0.1-0.2	4199
0.2-0.3	106
0.3-0.4	12
0.4-0.5	2
0.5-0.6	0
0.6-0.7	0
0.7-0.8	1
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
0.7143	Intermediate Similarity	NPD4381	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