NPASS Compound

Natural Product: NPC168496

Natural Product ID	NPC168496
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	QALQCLOCLGDLDQ-GTAZHCIVSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	n.a.
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000334] Flavonoids [CHEMONTID:0001111] Flavonoid glycosides [CHEMONTID:0001583] Flavonoid O-glycosides [CHEMONTID:0003533] Flavonoid-7-O-glycosides

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 52 55 0 0 0 0 0 0 0 0999 V2000 5.8173 1.5258 -0.0084 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2419 0.7462 -1.2080 C 0 0 1 0 0 0 0 0 0 0 0 0 5.3304 -0.3935 -1.5366 C 0 0 1 0 0 0 0 0 0 0 0 0 5.4683 -1.5695 -0.6253 C 0 0 2 0 0 0 0 0 0 0 0 0 3.9893 -1.9764 -0.4735 C 0 0 2 0 0 0 0 0 0 0 0 0 3.3897 -0.5587 -0.5328 C 0 0 2 0 0 0 0 0 0 0 0 0 2.0333 -0.6866 -0.8074 O 0 0 0 0 0 0 0 0 0 0 0 0 1.0087 -0.1768 -0.0441 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1751 0.5442 1.1188 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0956 1.0392 1.8556 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1885 0.8084 1.4198 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3882 0.0914 0.2617 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3018 -0.3968 -0.4638 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5981 -0.1381 -0.1680 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7090 0.2659 0.4214 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9768 -0.0816 -0.2002 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9639 -0.8247 -1.3892 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.1232 -1.1866 -2.0284 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.3715 -0.8512 -1.5558 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.4069 -0.1242 -0.3939 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.2202 0.2475 0.2624 C 0 0 0 0 0 0 0 0 0 0 0 0 -8.6346 0.2451 0.1340 O 0 0 0 0 0 0 0 0 0 0 0 0 -8.5205 -1.2382 -2.2347 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5544 0.9783 1.5700 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2896 1.2695 2.1012 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.1620 1.9266 3.1599 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.6356 1.4522 2.2729 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2646 1.7642 3.0250 O 0 0 0 0 0 0 0 0 0 0 0 0 4.0003 -0.0591 -1.6732 O 0 0 0 0 0 0 0 0 0 0 0 0 3.7952 -2.4954 0.7852 O 0 0 0 0 0 0 0 0 0 0 0 0 6.0684 -1.2784 0.5664 O 0 0 0 0 0 0 0 0 0 0 0 0 6.1542 1.6419 -2.3225 O 0 0 0 0 0 0 0 0 0 0 0 0 5.7484 0.9375 0.8991 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8073 1.9663 -0.2361 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5193 2.3912 0.0831 H 0 0 0 0 0 0 0 0 0 0 0 0 7.2885 0.3929 -1.1560 H 0 0 0 0 0 0 0 0 0 0 0 0 5.6019 -0.7857 -2.5966 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9318 -2.4410 -1.1478 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6405 -2.5861 -1.3034 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6288 -0.0001 0.3736 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1656 0.7419 1.4863 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.4425 -0.9570 -1.3679 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.9840 -1.1090 -1.7937 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0852 -1.7662 -2.9543 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.3105 0.8130 1.1630 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.8933 1.2353 0.0105 H 0 0 0 0 0 0 0 0 0 0 0 0 -9.2715 -1.7405 -1.7788 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6597 1.4339 3.2938 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2319 2.7648 3.0888 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8794 -2.3658 1.1095 H 0 0 0 0 0 0 0 0 0 0 0 0 6.8901 -1.8110 0.7122 H 0 0 0 0 0 0 0 0 0 0 0 0 5.5256 2.3751 -2.1082 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 2 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 1 0 16 17 2 0 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 20 22 1 0 19 23 1 0 15 24 2 0 24 25 1 0 25 26 2 0 24 27 1 0 10 28 1 0 6 29 1 0 5 30 1 0 4 31 1 0 2 32 1 0 29 3 1 0 13 8 1 0 21 16 1 0 25 11 1 0 1 33 1 0 1 34 1 0 1 35 1 0 2 36 1 1 3 37 1 6 4 38 1 6 5 39 1 6 6 40 1 1 9 41 1 0 13 42 1 0 17 43 1 0 18 44 1 0 21 45 1 0 22 46 1 0 23 47 1 0 27 48 1 0 28 49 1 0 30 50 1 0 31 51 1 0 32 52 1 0 M END

Standard InCHIKey	QALQCLOCLGDLDQ-GTAZHCIVSA-N
Standard InCHI	InChI=1S/C21H20O11/c1-7(22)19-17(28)18(29)21(32-19)30-9-5-12(25)14-13(6-9)31-20(16(27)15(14)26)8-2-3-10(23)11(24)4-8/h2-7,17-19,21-25,27-29H,1H3/t7-,17-,18+,19-,21+/m0/s1
SMILES	C[C@@H]([C@H]1[C@H]([C@H]([C@H](Oc2cc(c3c(c2)oc(c2ccc(c(c2)O)O)c(c3=O)O)O)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	448.1	Volume:	413.147 ? Van der Waals volume.
Dense:	1.085	LogP:	0.777 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.066 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.218 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	4.0	Rigid Bonds:	23.0
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:	0.275	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.109	Fsp³:	0.286
MCE-18:	89.0 ? 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:	0.63	Fluc inhibitor:	0.361 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.971 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.887 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.248	Promiscuous compounds:	0.812

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.3	MDCK Permeability:	-4.962
Pgp-inhibitor:	0.001	Pgp-substrate:	0.05
PAMPA:	0.994 ? 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):	0.963
20% Bioavailability (F20%):	0.975	30% Bioavailability (F30%):	1.0
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.902
Plasma Protein Binding (PPB):	81.065%	Volume Distribution (VD):	-0.315
Fu:	15.294% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.972
OATP1B3 inhibitor:	0.999	BCRP inhibitor:	0.481
BSEP inhibitor:	0.002

ADMET: Metabolism

CYP1A2-inhibitor:	0.166	CYP1A2-substrate:	0.004
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.086
CYP2C9-inhibitor:	0.008	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.176
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.369
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.375
HLM stability:	0.507 ? 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):

3.709

Half-life (T1/2):

3.191

ADMET: Toxicity

hERG Blockers:	0.022	hERG Blockers (10um):	0.224
Human Hepatotoxicity (H-HT):	0.607	Drug-induced Liver Injury (DILI):	0.981
AMES Toxicity:	0.905	Rat Oral Acute Toxicity:	0.175
Maximum Recommended Daily Dose:	0.302	Skin Sensitization:	0.999
Carcinogencity:	0.207	Eye Corrosion:	0.001
Eye Irritation:	0.958	Respiratory Toxicity:	0.374
Drug-induced Neurotoxicity:	0.016	Ototoxicity:	0.644
Hematotoxicity:	0.217	Drug-induced Nephrotoxicity:	0.196
Genotoxicity:	0.962	RPMI-8226 Immunitoxicity:	0.094
A549 Cytotoxicity:	0.986	Hek293 Cytotoxicity:	0.583
BCF:	0.638 ? 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:	3.361 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.699 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.137 ? 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
NPO22602	Pityrogramma tartarea	Species	Pteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20977	Capparis masaikai	Species	Capparaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20977	Capparis masaikai	Species	Capparaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21260	Nectandra pichurim	Species	Lauraceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO22602	Pityrogramma tartarea	Species	Pteridaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20977	Capparis masaikai	Species	Capparaceae	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 NPC168496 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	18869
0.1-0.2	27413
0.2-0.3	2590
0.3-0.4	599
0.4-0.5	297
0.5-0.6	66
0.6-0.7	16
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	NPC238376
0.7887	Intermediate Similarity	NPC277205
0.7887	Intermediate Similarity	NPC37919
0.726	Intermediate Similarity	NPC108831
0.726	Intermediate Similarity	NPC182634
0.7125	Intermediate Similarity	NPC67105
0.6933	Remote Similarity	NPC323593
0.6933	Remote Similarity	NPC203500
0.6875	Remote Similarity	NPC87125
0.6456	Remote Similarity	NPC285197
0.6364	Remote Similarity	NPC19709
0.631	Remote Similarity	NPC227508
0.625	Remote Similarity	NPC307938
0.622	Remote Similarity	NPC601586
0.6203	Remote Similarity	NPC271692
0.6173	Remote Similarity	NPC486578
0.6118	Remote Similarity	NPC275454
0.6076	Remote Similarity	NPC136042
0.6076	Remote Similarity	NPC189142
0.6076	Remote Similarity	NPC77660
0.6	Remote Similarity	NPC245014
0.6	Remote Similarity	NPC84362
0.5926	Remote Similarity	NPC117260
0.5904	Remote Similarity	NPC605784
0.5882	Remote Similarity	NPC143799
0.5882	Remote Similarity	NPC605755
0.5833	Remote Similarity	NPC190003
0.575	Remote Similarity	NPC249281
0.5682	Remote Similarity	NPC210073
0.5679	Remote Similarity	NPC282987
0.5679	Remote Similarity	NPC609879
0.5652	Remote Similarity	NPC80068
0.5625	Remote Similarity	NPC473043
0.5625	Remote Similarity	NPC331652
0.561	Remote Similarity	NPC46420
0.5556	Remote Similarity	NPC254306
0.5556	Remote Similarity	NPC252933
0.5507	Remote Similarity	NPC152042
0.5506	Remote Similarity	NPC233994
0.5495	Remote Similarity	NPC65711
0.5493	Remote Similarity	NPC200740
0.5488	Remote Similarity	NPC297987
0.5488	Remote Similarity	NPC158674
0.5435	Remote Similarity	NPC139060
0.5366	Remote Similarity	NPC39360
0.5366	Remote Similarity	NPC476405
0.5366	Remote Similarity	NPC29763
0.5366	Remote Similarity	NPC210003
0.5349	Remote Similarity	NPC116458
0.5349	Remote Similarity	NPC246943
0.5341	Remote Similarity	NPC8856
0.5326	Remote Similarity	NPC211532
0.5326	Remote Similarity	NPC488364
0.5309	Remote Similarity	NPC67037
0.5309	Remote Similarity	NPC255615
0.5306	Remote Similarity	NPC480796
0.5294	Remote Similarity	NPC179271
0.5287	Remote Similarity	NPC276377
0.5278	Remote Similarity	NPC166753
0.5275	Remote Similarity	NPC115674
0.5269	Remote Similarity	NPC229409
0.5238	Remote Similarity	NPC84265
0.5233	Remote Similarity	NPC197285
0.5211	Remote Similarity	NPC188871
0.5208	Remote Similarity	NPC135358
0.519	Remote Similarity	NPC473241
0.5181	Remote Similarity	NPC289667
0.5181	Remote Similarity	NPC127546
0.5181	Remote Similarity	NPC261866
0.5181	Remote Similarity	NPC57625
0.5181	Remote Similarity	NPC173637
0.5181	Remote Similarity	NPC317489
0.5181	Remote Similarity	NPC223424
0.5181	Remote Similarity	NPC600591
0.5176	Remote Similarity	NPC21100
0.5176	Remote Similarity	NPC27942
0.5169	Remote Similarity	NPC606546
0.5158	Remote Similarity	NPC188815
0.5147	Remote Similarity	NPC20791
0.5139	Remote Similarity	NPC108406
0.5116	Remote Similarity	NPC20505
0.5116	Remote Similarity	NPC611303
0.5109	Remote Similarity	NPC186816
0.5057	Remote Similarity	NPC601144
0.5056	Remote Similarity	NPC477848
0.5055	Remote Similarity	NPC44931
0.5053	Remote Similarity	NPC486577
0.5052	Remote Similarity	NPC484301

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC168496 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4966
0.1-0.2	4123
0.2-0.3	48
0.3-0.4	8
0.4-0.5	3
0.5-0.6	2
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
0.5158	Remote Similarity	NPD7251	Phase 2
0.5147	Remote Similarity	NPD1512	Phase 3

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