NPASS Compound

Natural Product: NPC305454

Natural Product ID	NPC305454
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZOZXCTSYNLVRKO-OTHOSUPWSA-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

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 0.7707 0.2768 0.1719 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6107 0.1902 -0.0375 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.1352 0.3478 -1.2952 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2264 0.5941 -2.3287 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1310 0.6791 -2.1224 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6519 0.5194 -0.8537 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1174 0.6093 -0.6183 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5121 1.9182 0.0198 C 0 0 2 0 0 0 0 0 0 0 0 0 5.0125 1.9215 0.0879 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6676 2.9766 -0.0754 O 0 0 0 0 0 0 0 0 0 0 0 0 5.6879 0.6527 0.3513 C 0 0 0 0 0 0 0 0 0 0 0 0 7.0643 0.6325 0.5306 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6910 -0.5738 0.7790 C 0 0 0 0 0 0 0 0 0 0 0 0 6.9799 -1.7533 0.8521 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6041 -1.7203 0.6710 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9455 -0.5242 0.4199 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5753 -0.4432 0.2328 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5772 -2.9678 1.0979 O 0 0 0 0 0 0 0 0 0 0 0 0 7.7929 1.8330 0.4569 O 0 0 0 0 0 0 0 0 0 0 0 0 3.0641 2.0173 1.3289 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.4854 0.2750 -1.5733 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5147 0.0412 -0.6780 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.5857 1.1395 -0.7265 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.5428 0.8275 0.4030 C 0 0 2 0 0 0 0 0 0 0 0 0 -5.4956 -0.5845 0.8682 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.0699 -1.5818 -0.1449 C 0 0 1 0 0 0 0 0 0 0 0 0 -6.2488 -2.2406 -0.8590 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.1830 -2.7195 0.0467 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1701 -1.1222 -1.0766 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.7332 -0.7260 2.0510 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8380 1.2544 0.1139 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.0186 2.4024 -0.6051 O 0 0 0 0 0 0 0 0 0 0 0 0 1.1624 0.1471 1.1856 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.2621 -0.0029 0.8059 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.6448 0.7170 -3.3146 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8380 0.8697 -2.9203 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6111 0.5456 -1.6077 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1614 2.7887 -0.5419 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7705 -0.6140 0.9231 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0076 -2.6074 0.7180 H 0 0 0 0 0 0 0 0 0 0 0 0 7.7447 -3.6548 0.3600 H 0 0 0 0 0 0 0 0 0 0 0 0 8.0707 2.3400 1.2816 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5847 1.4335 1.9290 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2241 -0.1003 0.3794 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1382 0.9989 -1.6767 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.2060 1.4724 1.2677 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.5434 -0.8610 1.1886 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5558 -2.4227 0.4084 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7753 -1.4702 -1.4760 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8859 -3.0865 -1.4606 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7905 -2.9286 0.9361 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3701 -1.6465 2.0485 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.1813 0.8949 -0.7421 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3609 3.0358 -1.3050 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 7 8 1 0 8 9 1 0 9 10 2 0 9 11 1 0 11 12 2 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 2 0 16 17 1 0 14 18 1 0 12 19 1 0 8 20 1 0 3 21 1 0 21 22 1 0 22 23 1 0 23 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 26 29 1 0 25 30 1 0 24 31 1 0 23 32 1 0 6 1 1 0 17 7 1 0 29 22 1 0 16 11 1 0 1 33 1 0 2 34 1 0 4 35 1 0 5 36 1 0 7 37 1 6 8 38 1 6 13 39 1 0 15 40 1 0 18 41 1 0 19 42 1 0 20 43 1 0 22 44 1 1 23 45 1 6 24 46 1 1 25 47 1 1 26 48 1 1 27 49 1 0 27 50 1 0 28 51 1 0 30 52 1 0 31 53 1 0 32 54 1 0 M END

Standard InCHIKey	ZOZXCTSYNLVRKO-OTHOSUPWSA-N
Standard InCHI	InChI=1S/C21H22O11/c22-7-13-15(25)17(27)19(29)21(32-13)30-10-3-1-8(2-4-10)20-18(28)16(26)14-11(24)5-9(23)6-12(14)31-20/h1-6,13,15,17-25,27-29H,7H2/t13-,15-,17+,18+,19-,20+,21-/m1/s1
SMILES	c1cc(ccc1[C@H]1[C@H](C(=O)c2c(cc(cc2O1)O)O)O)O[C@H]1[C@@H]([C@H]([C@@H]([C@@H](CO)O1)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	450.12	Volume:	415.784 ? Van der Waals volume.
Dense:	1.083	LogP:	-0.06 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.627 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.491 ? 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:	0.301	GASA:	0.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.157	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:	0	PAINS Alert:	0
Colloidal aggregators:	0.58	Fluc inhibitor:	0.511 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.06 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.291 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.413	Promiscuous compounds:	0.382

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.752	MDCK Permeability:	-4.934
Pgp-inhibitor:	0.01	Pgp-substrate:	0.503
PAMPA:	0.986 ? 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):	0.208
20% Bioavailability (F20%):	0.017	30% Bioavailability (F30%):	0.994
50% Bioavailability (F50%):	0.993

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.166
Plasma Protein Binding (PPB):	91.257%	Volume Distribution (VD):	-0.161
Fu:	8.322% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	1.0
OATP1B3 inhibitor:	1.0	BCRP inhibitor:	0.404
BSEP inhibitor:	0.014

ADMET: Metabolism

CYP1A2-inhibitor:	0.614	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.006
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.0
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.138
HLM stability:	0.002 ? 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):

3.067

Half-life (T1/2):

3.762

ADMET: Toxicity

hERG Blockers:	0.024	hERG Blockers (10um):	0.139
Human Hepatotoxicity (H-HT):	0.878	Drug-induced Liver Injury (DILI):	0.954
AMES Toxicity:	0.978	Rat Oral Acute Toxicity:	0.074
Maximum Recommended Daily Dose:	0.064	Skin Sensitization:	0.987
Carcinogencity:	0.215	Eye Corrosion:	0.0
Eye Irritation:	0.586	Respiratory Toxicity:	0.069
Drug-induced Neurotoxicity:	0.008	Ototoxicity:	0.969
Hematotoxicity:	0.321	Drug-induced Nephrotoxicity:	0.886
Genotoxicity:	0.98	RPMI-8226 Immunitoxicity:	0.156
A549 Cytotoxicity:	0.377	Hek293 Cytotoxicity:	0.508
BCF:	0.395 ? 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:	3.13 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.59 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.752 ? 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
NPO29504	Urena lobata	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO29504	Urena lobata	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO29504	Urena lobata	Species	Malvaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO29504	Urena lobata	Species	Malvaceae	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 NPC305454 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	21073
0.1-0.2	24422
0.2-0.3	3253
0.3-0.4	796
0.4-0.5	240
0.5-0.6	53
0.6-0.7	14
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	Natural Product ID
0.75	Intermediate Similarity	NPC26195
0.6721	Remote Similarity	NPC44721
0.6721	Remote Similarity	NPC211466
0.6721	Remote Similarity	NPC605332
0.662	Remote Similarity	NPC163191
0.6418	Remote Similarity	NPC477240
0.6364	Remote Similarity	NPC106025
0.6176	Remote Similarity	NPC199335
0.6129	Remote Similarity	NPC62290
0.6129	Remote Similarity	NPC142731
0.6129	Remote Similarity	NPC326506
0.6129	Remote Similarity	NPC4152
0.6087	Remote Similarity	NPC190217
0.6027	Remote Similarity	NPC160156
0.6027	Remote Similarity	NPC92565
0.5946	Remote Similarity	NPC170475
0.5823	Remote Similarity	NPC259834
0.5733	Remote Similarity	NPC259182
0.5733	Remote Similarity	NPC88484
0.5714	Remote Similarity	NPC21835
0.5672	Remote Similarity	NPC320825
0.5658	Remote Similarity	NPC219163
0.5606	Remote Similarity	NPC36835
0.5606	Remote Similarity	NPC246162
0.5606	Remote Similarity	NPC9743
0.5606	Remote Similarity	NPC260491
0.5606	Remote Similarity	NPC61506
0.5606	Remote Similarity	NPC240476
0.5606	Remote Similarity	NPC250922
0.5584	Remote Similarity	NPC257963
0.5538	Remote Similarity	NPC19721
0.5517	Remote Similarity	NPC168789
0.5507	Remote Similarity	NPC326037
0.5507	Remote Similarity	NPC13858
0.5455	Remote Similarity	NPC214454
0.5455	Remote Similarity	NPC39351
0.5441	Remote Similarity	NPC23084
0.5397	Remote Similarity	NPC294470
0.5385	Remote Similarity	NPC279417
0.5385	Remote Similarity	NPC208176
0.5385	Remote Similarity	NPC49130
0.5362	Remote Similarity	NPC26080
0.5362	Remote Similarity	NPC165686
0.5333	Remote Similarity	NPC259767
0.5325	Remote Similarity	NPC97052
0.5323	Remote Similarity	NPC212729
0.5323	Remote Similarity	NPC142319
0.5323	Remote Similarity	NPC604498
0.525	Remote Similarity	NPC36916
0.525	Remote Similarity	NPC36
0.525	Remote Similarity	NPC7154
0.525	Remote Similarity	NPC125039
0.525	Remote Similarity	NPC7688
0.5238	Remote Similarity	NPC269242
0.5224	Remote Similarity	NPC306607
0.5195	Remote Similarity	NPC169248
0.5195	Remote Similarity	NPC72649
0.5185	Remote Similarity	NPC138688
0.5185	Remote Similarity	NPC72787
0.5185	Remote Similarity	NPC217795
0.5185	Remote Similarity	NPC58223
0.5125	Remote Similarity	NPC29830
0.5125	Remote Similarity	NPC181014
0.5067	Remote Similarity	NPC121001
0.5065	Remote Similarity	NPC153342
0.5062	Remote Similarity	NPC5778
0.5059	Remote Similarity	NPC152346
0.5059	Remote Similarity	NPC197703

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC305454 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	4987
0.1-0.2	4054
0.2-0.3	89
0.3-0.4	16
0.4-0.5	1
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
0.525	Remote Similarity	NPD6166	Phase 2
0.525	Remote Similarity	NPD6167	Clinical (unspecified phase)
0.525	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