NPASS Compound

Natural Product: NPC535975

Natural Product ID	NPC535975
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	(2~{S})-5,7-dihydroxy-2-[3-hydroxy-4-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]chroman-4-one
IUPAC Name	(2~{S})-5,7-dihydroxy-2-[3-hydroxy-4-[(2~{S},3~{R},4~{S},5~{S},6~{R})-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydropyran-2-yl]oxy-phenyl]chroman-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 54 57 0 0 0 0 0 0 0 0999 V2000 5.5097 -1.6624 2.4631 O 0 0 0 0 0 0 0 0 0 0 0 0 4.9859 -0.7885 1.7587 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5446 -0.4326 1.7886 C 0 0 0 0 0 0 0 0 0 0 0 0 3.0854 -0.3480 0.3449 C 0 0 1 0 0 0 0 0 0 0 0 0 1.6313 -0.2337 0.2227 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8852 -1.3280 -0.1562 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.5066 -1.2591 -0.2843 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1738 -0.0806 -0.0317 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5158 0.1229 -0.1177 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5243 -0.7745 -0.4703 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.2030 -0.4325 -1.6181 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3297 0.3188 -1.4828 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.0476 1.8032 -1.2296 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.3264 2.0305 -0.0908 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3611 -0.2083 -0.5342 C 0 0 1 0 0 0 0 0 0 0 0 0 -7.5551 -0.5682 -1.1575 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.8148 -1.4315 0.1437 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.6792 -1.8028 1.1565 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.4607 -1.0686 0.7009 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.0157 -2.2047 1.4161 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3921 1.0034 0.3481 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.9835 2.2420 0.6252 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9745 0.9312 0.4727 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7767 0.7374 -0.2449 O 0 0 0 0 0 0 0 0 0 0 0 0 5.1760 0.7041 -0.1537 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9642 1.4191 -1.0456 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3396 1.3927 -0.9642 C 0 0 0 0 0 0 0 0 0 0 0 0 8.1297 2.1206 -1.8726 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9546 0.6452 0.0182 C 0 0 0 0 0 0 0 0 0 0 0 0 7.2085 -0.0790 0.9235 C 0 0 0 0 0 0 0 0 0 0 0 0 7.7937 -0.8487 1.9332 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8291 -0.0290 0.8114 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9407 -1.1629 2.3481 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4664 0.5928 2.2068 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4651 -1.2751 -0.1532 H 0 0 0 0 0 0 0 0 0 0 0 0 1.4117 -2.2501 -0.3534 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0653 -2.1344 -0.5833 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.0387 -1.7520 -0.6872 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8241 0.3153 -2.5027 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9716 2.3804 -1.3317 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3970 2.1140 -2.0979 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8269 2.0442 0.7434 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6259 0.5179 0.2658 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.2010 0.1956 -1.0816 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6581 -2.2574 -0.5787 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3011 -2.4648 1.7779 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4869 -0.2512 1.4332 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2321 -2.0037 1.9656 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3872 2.4318 1.5509 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5763 1.7986 0.7741 H 0 0 0 0 0 0 0 0 0 0 0 0 5.4647 1.9975 -1.8065 H 0 0 0 0 0 0 0 0 0 0 0 0 8.9795 2.5128 -1.4907 H 0 0 0 0 0 0 0 0 0 0 0 0 9.0409 0.6270 0.0792 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7714 -1.8667 1.7707 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 2 0 6 7 1 0 7 8 2 0 8 9 1 0 9 10 1 0 10 11 1 0 11 12 1 0 12 13 1 0 13 14 1 0 12 15 1 0 15 16 1 0 15 17 1 0 17 18 1 0 17 19 1 0 19 20 1 0 8 21 1 0 21 22 1 0 21 23 2 0 4 24 1 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 1 0 27 29 2 0 29 30 1 0 30 31 1 0 30 32 2 0 32 2 1 0 23 5 1 0 32 25 1 0 19 10 1 0 3 33 1 0 3 34 1 0 4 35 1 6 6 36 1 0 7 37 1 0 10 38 1 6 12 39 1 6 13 40 1 0 13 41 1 0 14 42 1 0 15 43 1 1 16 44 1 0 17 45 1 6 18 46 1 0 19 47 1 1 20 48 1 0 22 49 1 0 23 50 1 0 26 51 1 0 28 52 1 0 29 53 1 0 31 54 1 0 M END

Standard InCHIKey	ZKMIRYADZQAFFT-SFTVRKLSSA-N
Standard InCHI	InChI=1S/C21H22O11/c22-7-16-18(27)19(28)20(29)21(32-16)31-13-2-1-8(3-10(13)24)14-6-12(26)17-11(25)4-9(23)5-15(17)30-14/h1-5,14,16,18-25,27-29H,6-7H2/t14-,16+,18+,19-,20+,21+/m0/s1
SMILES	O=C1C[C@@H](C2=CC=C(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)C(O)=C2)OC2=CC(O)=CC(O)=C12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	450.12	Volume:	415.784 ? Van der Waals volume.
Dense:	1.083	LogP:	0.642 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.109 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.136 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	24.0
TPSA:	186.37 ? 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:	0.324	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.134	Fsp³:	0.381
MCE-18:	90.552 ? 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:	1
Chelating Alert:	1	PAINS Alert:	0
Colloidal aggregators:	0.608	Fluc inhibitor:	0.464 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.129 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.556 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.233	Promiscuous compounds:	0.333

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.69	MDCK Permeability:	-5.02
Pgp-inhibitor:	0.023	Pgp-substrate:	0.093
PAMPA:	0.953 ? 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):	0.338
20% Bioavailability (F20%):	0.008	30% Bioavailability (F30%):	0.999
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.166
Plasma Protein Binding (PPB):	88.212%	Volume Distribution (VD):	-0.147
Fu:	10.506% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.983
BSEP inhibitor:	0.007

ADMET: Metabolism

CYP1A2-inhibitor:	0.373	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.022
CYP2C9-inhibitor:	0.003	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.34
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.002
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.912
HLM stability:	0.706 ? 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):

3.304

Half-life (T1/2):

3.426

ADMET: Toxicity

hERG Blockers:	0.02	hERG Blockers (10um):	0.126
Human Hepatotoxicity (H-HT):	0.747	Drug-induced Liver Injury (DILI):	0.913
AMES Toxicity:	0.948	Rat Oral Acute Toxicity:	0.062
Maximum Recommended Daily Dose:	0.113	Skin Sensitization:	0.988
Carcinogencity:	0.431	Eye Corrosion:	0.0
Eye Irritation:	0.692	Respiratory Toxicity:	0.02
Drug-induced Neurotoxicity:	0.01	Ototoxicity:	0.879
Hematotoxicity:	0.157	Drug-induced Nephrotoxicity:	0.629
Genotoxicity:	0.989	RPMI-8226 Immunitoxicity:	0.149
A549 Cytotoxicity:	0.549	Hek293 Cytotoxicity:	0.628
BCF:	0.456 ? 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:	2.999 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.586 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.688 ? 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
NPO55911	Sedum sediforme	Species	Crassulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]

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 NPC535975 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	19220
0.1-0.2	25773
0.2-0.3	3716
0.3-0.4	851
0.4-0.5	235
0.5-0.6	41
0.6-0.7	14
0.7-0.8	0
0.8-0.85	1
0.85-0.9	0
0.9-0.95	0
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.8261	Intermediate Similarity	NPC26195
0.72	Intermediate Similarity	NPC5778
0.6623	Remote Similarity	NPC29830
0.6579	Remote Similarity	NPC219163
0.6579	Remote Similarity	NPC39351
0.6447	Remote Similarity	NPC97052
0.6375	Remote Similarity	NPC236934
0.6324	Remote Similarity	NPC302950
0.625	Remote Similarity	NPC199335
0.6234	Remote Similarity	NPC170475
0.6203	Remote Similarity	NPC181014
0.6164	Remote Similarity	NPC190217
0.6136	Remote Similarity	NPC168789
0.6104	Remote Similarity	NPC169248
0.6104	Remote Similarity	NPC72649
0.6027	Remote Similarity	NPC477240
0.5909	Remote Similarity	NPC70441
0.5875	Remote Similarity	NPC257963
0.5823	Remote Similarity	NPC45400
0.5823	Remote Similarity	NPC259182
0.5753	Remote Similarity	NPC106025
0.5667	Remote Similarity	NPC105095
0.5667	Remote Similarity	NPC177731
0.5667	Remote Similarity	NPC725
0.5556	Remote Similarity	NPC471457
0.5556	Remote Similarity	NPC44328
0.5556	Remote Similarity	NPC79056
0.5488	Remote Similarity	NPC206378
0.5484	Remote Similarity	NPC199079
0.5476	Remote Similarity	NPC477502
0.5455	Remote Similarity	NPC174953
0.5352	Remote Similarity	NPC321011
0.5352	Remote Similarity	NPC294852
0.5352	Remote Similarity	NPC188679
0.5309	Remote Similarity	NPC160156
0.5309	Remote Similarity	NPC92565
0.5294	Remote Similarity	NPC472383
0.5281	Remote Similarity	NPC105283
0.527	Remote Similarity	NPC236637
0.5263	Remote Similarity	NPC59324
0.5244	Remote Similarity	NPC88484
0.5217	Remote Similarity	NPC182421
0.5211	Remote Similarity	NPC274784
0.5211	Remote Similarity	NPC20709
0.5181	Remote Similarity	NPC474038
0.5143	Remote Similarity	NPC32441
0.5143	Remote Similarity	NPC243083
0.5143	Remote Similarity	NPC13768
0.5143	Remote Similarity	NPC287246
0.5143	Remote Similarity	NPC79943
0.5135	Remote Similarity	NPC19470
0.5116	Remote Similarity	NPC472381
0.5114	Remote Similarity	NPC158188
0.5067	Remote Similarity	NPC481303
0.5057	Remote Similarity	NPC602605
0.5054	Remote Similarity	NPC291124
0.5054	Remote Similarity	NPC131157

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC535975 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4687
0.1-0.2	4374
0.2-0.3	67
0.3-0.4	14
0.4-0.5	4
0.5-0.6	3
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
0.6324	Remote Similarity	NPD1934	Phase 0
0.5556	Remote Similarity	NPD7074	Phase 3
0.5143	Remote Similarity	NPD1550	Phase 2
0.5143	Remote Similarity	NPD1552	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