NPASS Compound

Natural Product: NPC604854

Natural Product ID	NPC604854
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ACRIYYKEWCXQOS-XAYOXWHSSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL4633520
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 68 72 0 0 0 0 0 0 0 0999 V2000 1.8743 -0.2410 3.0240 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4792 -0.0294 1.9522 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7282 0.6046 1.9158 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3793 0.8296 0.7314 C 0 0 0 0 0 0 0 0 0 0 0 0 5.6838 1.4888 0.6596 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3724 1.9389 1.7527 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6199 2.5626 1.6106 C 0 0 0 0 0 0 0 0 0 0 0 0 8.2059 2.7504 0.3803 C 0 0 0 0 0 0 0 0 0 0 0 0 9.4497 3.3722 0.2387 O 0 0 0 0 0 0 0 0 0 0 0 0 7.5166 2.2987 -0.7246 C 0 0 0 0 0 0 0 0 0 0 0 0 6.2911 1.6861 -0.5841 C 0 0 0 0 0 0 0 0 0 0 0 0 3.7748 0.4226 -0.3575 O 0 0 0 0 0 0 0 0 0 0 0 0 2.6057 -0.1776 -0.3982 C 0 0 0 0 0 0 0 0 0 0 0 0 2.0359 -0.5761 -1.5885 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8155 -1.2012 -1.6145 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2297 -1.6104 -2.8324 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1014 -1.4614 -0.4641 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.2170 -2.1401 -0.5292 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.1699 -3.0378 -1.5900 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1833 -3.9817 -1.5322 C 0 0 2 0 0 0 0 0 0 0 0 0 -2.3458 -4.5572 -2.9259 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6792 -3.5353 -3.8127 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.4831 -3.4064 -1.0784 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.7616 -3.7343 0.2589 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5761 -1.9146 -1.2118 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7619 -1.5036 -2.5308 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.3663 -1.1932 -0.6660 C 0 0 1 0 0 0 0 0 0 0 0 0 -2.7423 -0.6196 0.5461 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.6421 0.7607 0.5478 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.7356 1.2317 1.4617 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.2799 1.9920 2.4679 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9183 3.2741 1.9771 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.7665 3.7283 2.9807 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7493 2.9315 0.7718 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9759 3.6135 0.7656 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.9822 1.4347 0.7410 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.8455 1.1793 -0.3201 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6739 -1.0620 0.7213 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0032 -1.3002 1.9063 O 0 0 0 0 0 0 0 0 0 0 0 0 1.9147 -0.4249 0.7651 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1731 0.9158 2.8457 H 0 0 0 0 0 0 0 0 0 0 0 0 5.9446 1.8103 2.7445 H 0 0 0 0 0 0 0 0 0 0 0 0 8.1476 2.9106 2.4818 H 0 0 0 0 0 0 0 0 0 0 0 0 9.5713 4.3736 0.2208 H 0 0 0 0 0 0 0 0 0 0 0 0 7.9849 2.4499 -1.6955 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7412 1.3277 -1.4443 H 0 0 0 0 0 0 0 0 0 0 0 0 2.5687 -0.3869 -2.5010 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3258 -0.8971 -3.3024 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.3771 -2.7236 0.4196 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8434 -4.7974 -0.8466 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4033 -5.0294 -3.2842 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1982 -5.2906 -2.9611 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8728 -3.0053 -4.0407 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.3176 -3.8411 -1.6708 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2574 -4.5446 0.4669 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5164 -1.6069 -0.6695 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3713 -0.5996 -2.6547 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.0734 -0.3559 -1.3378 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2686 1.0694 -0.4702 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4407 2.3026 3.1390 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.9899 1.4416 3.1114 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.1951 4.0427 1.6958 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5916 4.1099 2.5858 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2553 3.1932 -0.1896 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.4587 3.2740 -0.0359 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4577 1.0684 1.6736 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6068 0.6064 -0.0278 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1226 -2.2102 2.3320 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 2 0 8 9 1 0 8 10 1 0 10 11 2 0 4 12 1 0 12 13 1 0 13 14 2 0 14 15 1 0 15 16 1 0 15 17 2 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 20 23 1 0 23 24 1 0 23 25 1 0 25 26 1 0 25 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 32 34 1 0 34 35 1 0 34 36 1 0 36 37 1 0 17 38 1 0 38 39 1 0 38 40 2 0 40 2 1 0 11 5 1 0 40 13 1 0 27 18 1 0 36 29 1 0 3 41 1 0 6 42 1 0 7 43 1 0 9 44 1 0 10 45 1 0 11 46 1 0 14 47 1 0 16 48 1 0 18 49 1 1 20 50 1 1 21 51 1 0 21 52 1 0 22 53 1 0 23 54 1 6 24 55 1 0 25 56 1 1 26 57 1 0 27 58 1 6 29 59 1 6 31 60 1 0 31 61 1 0 32 62 1 6 33 63 1 0 34 64 1 6 35 65 1 0 36 66 1 1 37 67 1 0 39 68 1 0 M END

Standard InCHIKey	ACRIYYKEWCXQOS-XAYOXWHSSA-N
Standard InCHI	InChI=1S/C26H28O14/c27-7-16-20(33)22(35)25(40-26-23(36)19(32)13(31)8-37-26)24(39-16)18-12(30)6-15-17(21(18)34)11(29)5-14(38-15)9-1-3-10(28)4-2-9/h1-6,13,16,19-20,22-28,30-36H,7-8H2/t13-,16+,19-,20+,22-,23+,24-,25+,26-/m0/s1
SMILES	O=c1cc(-c2ccc(O)cc2)oc2cc(O)c([C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O[C@@H]3OC[C@H](O)[C@H](O)[C@H]3O)c(O)c12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	564.15	Volume:	517.441 ? Van der Waals volume.
Dense:	1.09	LogP:	0.19 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	0.554 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.21 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	5.0	Rigid Bonds:	30.0
TPSA:	239.97 ? Topological Polar Surface Area.	H-Bond Acceptor:	14.0
H-Bond Donor:	9.0	Rings:	5.0
Heavy Atoms:	14.0

MedChem Properties

QED Drug-Likeness Score:	0.172	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.68	Fsp³:	0.423
MCE-18:	116.838 ? 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:	Accepted	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.63	Fluc inhibitor:	0.177 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.843 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.547 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.161	Promiscuous compounds:	0.444

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.494	MDCK Permeability:	-5.059
Pgp-inhibitor:	0.0	Pgp-substrate:	0.78
PAMPA:	1.0 ? 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):	0.801
20% Bioavailability (F20%):	0.842	30% Bioavailability (F30%):	0.998
50% Bioavailability (F50%):	0.998

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.002	MRP1:	0.644
Plasma Protein Binding (PPB):	84.755%	Volume Distribution (VD):	-0.042
Fu:	12.161% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.441
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.01
BSEP inhibitor:	0.004

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.002	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.429
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.217
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.914
HLM stability:	0.395 ? 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):

1.905

Half-life (T1/2):

3.219

ADMET: Toxicity

hERG Blockers:	0.01	hERG Blockers (10um):	0.063
Human Hepatotoxicity (H-HT):	0.645	Drug-induced Liver Injury (DILI):	0.955
AMES Toxicity:	0.935	Rat Oral Acute Toxicity:	0.04
Maximum Recommended Daily Dose:	0.086	Skin Sensitization:	0.999
Carcinogencity:	0.299	Eye Corrosion:	0.0
Eye Irritation:	0.872	Respiratory Toxicity:	0.072
Drug-induced Neurotoxicity:	0.002	Ototoxicity:	0.773
Hematotoxicity:	0.162	Drug-induced Nephrotoxicity:	0.31
Genotoxicity:	0.962	RPMI-8226 Immunitoxicity:	0.138
A549 Cytotoxicity:	0.837	Hek293 Cytotoxicity:	0.759
BCF:	0.389 ? 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:	2.794 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.313 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.494 ? 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
NPO27593	Silene dioica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO829	Vaccaria hispanica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO829	Vaccaria hispanica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO829	Vaccaria hispanica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TM-MC]
NPO829	Vaccaria hispanica	Species	Caryophyllaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO27593	Silene dioica	Species	Caryophyllaceae	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

Activity Type	# Activity
Activity	2

Activity Type	# Activity
Cell line	2

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
NPT2219	Cell line	C2C12	Mus musculus	Activity	n.a.	n.a.	n.a.	PMID[32527550]

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 NPC604854 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	22135
0.1-0.2	24175
0.2-0.3	2835
0.3-0.4	601
0.4-0.5	89
0.5-0.6	14
0.6-0.7	5
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
0.7442	Intermediate Similarity	NPC78734
0.6854	Remote Similarity	NPC47923
0.6506	Remote Similarity	NPC328740
0.6506	Remote Similarity	NPC289774
0.6087	Remote Similarity	NPC44947
0.6064	Remote Similarity	NPC218488
0.5682	Remote Similarity	NPC53545
0.5638	Remote Similarity	NPC294629
0.5638	Remote Similarity	NPC131407
0.5632	Remote Similarity	NPC611357
0.5612	Remote Similarity	NPC606547
0.551	Remote Similarity	NPC257566
0.5426	Remote Similarity	NPC111249
0.5361	Remote Similarity	NPC603300
0.5312	Remote Similarity	NPC190393
0.5172	Remote Similarity	NPC294863
0.5172	Remote Similarity	NPC282636
0.5111	Remote Similarity	NPC268193
0.5104	Remote Similarity	NPC326592
0.5104	Remote Similarity	NPC109594

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC604854 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5731
0.1-0.2	3350
0.2-0.3	59
0.3-0.4	10
0.4-0.5	0
0.5-0.6	0
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
		NPD

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