NPASS Compound

Natural Product: NPC488888

Natural Product ID	NPC488888
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	RQOWLXQAJIAZMF-RVKTWDRCSA-N
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	n.a.
PubChem CID	13932613
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000261] Phenylpropanoids and polyketides [CHEMONTID:0000238] Tannins [CHEMONTID:0001710] Hydrolyzable tannins

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 67 71 0 0 0 0 0 0 0 0999 V2000 5.2263 -0.1711 1.3416 C 0 0 0 0 0 0 0 0 0 0 0 0 4.6986 -1.2001 0.5927 C 0 0 0 0 0 0 0 0 0 0 0 0 5.2891 -2.4381 0.7033 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3806 -2.6215 1.5485 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8859 -1.5693 2.2861 C 0 0 0 0 0 0 0 0 0 0 0 0 6.3055 -0.3292 2.1845 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8459 0.7003 2.9441 O 0 0 0 0 0 0 0 0 0 0 0 0 7.9900 -1.7751 3.1349 O 0 0 0 0 0 0 0 0 0 0 0 0 6.9726 -3.8583 1.6608 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5569 -0.9397 -0.2706 C 0 0 0 0 0 0 0 0 0 0 0 0 3.1034 -1.8866 -0.9336 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9193 0.2332 -0.4397 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8482 0.5818 -1.2179 C 0 0 2 0 0 0 0 0 0 0 0 0 2.3767 1.4591 -2.3655 C 0 0 2 0 0 0 0 0 0 0 0 0 2.5439 2.8267 -1.7417 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2564 3.6810 -2.6101 O 0 0 0 0 0 0 0 0 0 0 0 0 1.3089 3.3527 -1.5688 O 0 0 0 0 0 0 0 0 0 0 0 0 0.2607 2.5432 -1.3069 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6146 3.3090 -0.2959 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6426 2.5648 0.2287 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.7366 2.1338 -0.4573 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.9374 2.3642 -1.6249 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.7815 1.3410 0.2326 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6025 2.2721 0.9141 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.5990 1.8813 1.7496 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8029 0.5280 1.9292 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.9981 -0.3449 1.2566 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9595 0.0324 0.3766 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3389 -1.0807 -0.3252 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0563 -1.4289 -0.4249 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6740 -2.6156 -1.0732 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5815 -3.4724 -1.6414 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9012 -3.1325 -1.5595 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2590 -1.9726 -0.9220 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.6124 -1.5925 -0.8368 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8722 -3.9421 -2.1098 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1601 -4.6511 -2.2807 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.8452 -0.6525 -0.0619 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.2087 -1.0158 0.9202 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.4639 0.4079 -0.8057 O 0 0 0 0 0 0 0 0 0 0 0 0 0.6639 1.2126 -0.6104 C 0 0 1 0 0 0 0 0 0 0 0 0 -5.2096 -1.6895 1.4593 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.8182 0.0696 2.7865 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.4200 2.7607 2.4287 O 0 0 0 0 0 0 0 0 0 0 0 0 1.5358 1.4488 -3.4559 O 0 0 0 0 0 0 0 0 0 0 0 0 4.7897 0.8096 1.2799 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9205 -3.2670 0.1465 H 0 0 0 0 0 0 0 0 0 0 0 0 6.5849 1.6687 2.8021 H 0 0 0 0 0 0 0 0 0 0 0 0 8.7646 -1.1192 3.1255 H 0 0 0 0 0 0 0 0 0 0 0 0 7.8806 -4.0862 1.3187 H 0 0 0 0 0 0 0 0 0 0 0 0 1.5373 -0.3415 -1.7567 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3984 1.1048 -2.6629 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0989 2.6869 -0.7925 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2051 3.3720 -2.5495 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2630 2.2682 -2.2110 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0949 4.1862 -0.8281 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0360 3.8019 0.4633 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4173 3.3368 0.7182 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.5976 -2.8331 -1.0901 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8437 -0.7729 -1.4172 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0652 -3.8713 -3.1007 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3635 -5.5561 -1.9095 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7162 1.4799 0.4369 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.0411 -2.0802 1.8333 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6445 0.6231 2.8171 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.2707 3.0958 2.0063 H 0 0 0 0 0 0 0 0 0 0 0 0 1.7964 2.1695 -4.0511 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 5 8 1 0 4 9 1 0 2 10 1 0 10 11 2 0 10 12 1 0 12 13 1 0 13 14 1 0 14 15 1 0 15 16 1 0 15 17 1 0 17 18 1 0 18 19 1 0 19 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 2 0 24 25 1 0 25 26 2 0 26 27 1 0 27 28 2 0 28 29 1 0 29 30 2 0 30 31 1 0 31 32 2 0 32 33 1 0 33 34 2 0 34 35 1 0 33 36 1 0 32 37 1 0 30 38 1 0 38 39 2 0 38 40 1 0 40 41 1 0 27 42 1 0 26 43 1 0 25 44 1 0 14 45 1 0 6 1 1 0 41 13 1 0 41 18 1 0 28 23 1 0 34 29 1 0 1 46 1 0 3 47 1 0 7 48 1 0 8 49 1 0 9 50 1 0 13 51 1 6 14 52 1 6 15 53 1 0 16 54 1 0 18 55 1 6 19 56 1 0 19 57 1 0 24 58 1 0 31 59 1 0 35 60 1 0 36 61 1 0 37 62 1 0 41 63 1 1 42 64 1 0 43 65 1 0 44 66 1 0 45 67 1 0 M END

Standard InCHIKey	RQOWLXQAJIAZMF-RVKTWDRCSA-N
Standard InCHI	InChI=1S/C27H22O18/c28-9-1-6(2-10(29)16(9)32)24(38)45-23-21(37)27(41)43-13-5-42-25(39)7-3-11(30)17(33)19(35)14(7)15-8(26(40)44-22(13)23)4-12(31)18(34)20(15)36/h1-4,13,21-23,27-37,41H,5H2/t13-,21-,22-,23-,27?/m1/s1
SMILES	c1c(cc(c(c1O)O)O)C(=O)O[C@@H]1[C@H](C(O)O[C@@H]2COC(=O)c3cc(c(c(c3-c3c(cc(c(c3O)O)O)C(=O)O[C@@H]12)O)O)O)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	634.08	Volume:	559.352 ? Van der Waals volume.
Dense:	1.134	LogP:	-0.8 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	-0.673 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.522 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	3.0	Rigid Bonds:	35.0
TPSA:	310.66 ? Topological Polar Surface Area.	H-Bond Acceptor:	18.0
H-Bond Donor:	11.0	Rings:	5.0
Heavy Atoms:	18.0

MedChem Properties

QED Drug-Likeness Score:	0.098	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.151	Fsp³:	0.222
MCE-18:	124.455 ? 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:	1
Chelating Alert:	1	PAINS Alert:	1
Colloidal aggregators:	0.911	Fluc inhibitor:	0.032 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.418 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.606 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.398	Promiscuous compounds:	0.985

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-6.823	MDCK Permeability:	-4.819
Pgp-inhibitor:	0.0	Pgp-substrate:	0.07
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):	0.0
20% Bioavailability (F20%):	0.602	30% Bioavailability (F30%):	0.752
50% Bioavailability (F50%):	0.822

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	1.0
Plasma Protein Binding (PPB):	62.265%	Volume Distribution (VD):	-0.248
Fu:	31.315% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.979
OATP1B3 inhibitor:	0.962	BCRP inhibitor:	0.148
BSEP inhibitor:	0.001

ADMET: Metabolism

CYP1A2-inhibitor:	0.0	CYP1A2-substrate:	0.0
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.0
CYP2C9-inhibitor:	0.0	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.862
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.887
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.736
HLM stability:	0.017 ? 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):

5.13

Half-life (T1/2):

3.556

ADMET: Toxicity

hERG Blockers:	0.007	hERG Blockers (10um):	0.913
Human Hepatotoxicity (H-HT):	0.506	Drug-induced Liver Injury (DILI):	0.994
AMES Toxicity:	0.987	Rat Oral Acute Toxicity:	0.157
Maximum Recommended Daily Dose:	0.813	Skin Sensitization:	1.0
Carcinogencity:	0.484	Eye Corrosion:	0.003
Eye Irritation:	0.993	Respiratory Toxicity:	0.025
Drug-induced Neurotoxicity:	0.0	Ototoxicity:	0.996
Hematotoxicity:	0.013	Drug-induced Nephrotoxicity:	0.04
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.002
A549 Cytotoxicity:	1.0	Hek293 Cytotoxicity:	0.196
BCF:	0.266 ? 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:	3.091 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.103 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.994 ? 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
NPO20417	Tamarix nilotica	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[20405847]
NPO20417	Tamarix nilotica	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[23675651]
NPO20417	Tamarix nilotica	Species	Tamaricaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[26938659]
NPO20786	Tamarix tetrandra	Species	Tamaricaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[26938659]
NPO20417	Tamarix nilotica	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20786	Tamarix tetrandra	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO20417	Tamarix nilotica	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO20417	Tamarix nilotica	Species	Tamaricaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO20786	Tamarix tetrandra	Species	Tamaricaceae	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
CC50	7

Activity Type	# Activity
Cell line	4
Others	3

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
NPT116	Cell line	HL-60	Homo sapiens	CC50	=	30500.0	nM	PMID[26938659]
NPT2394	Cell line	HSC-4	Homo sapiens	CC50	=	34400.0	nM	PMID[26938659]
NPT2385	Cell line	HSC-3	Homo sapiens	CC50	=	23300.0	nM	PMID[26938659]
NPT924	Cell line	HSC-2	Homo sapiens	CC50	=	5820.0	nM	PMID[26938659]
NPT2	Others	Unspecified	n.a.	CC50	>	100000.0	nM	PMID[26938659]

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 NPC488888 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	19102
0.1-0.2	29790
0.2-0.3	788
0.3-0.4	59
0.4-0.5	83
0.5-0.6	21
0.6-0.7	6
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
0.7213	Intermediate Similarity	NPC175793
0.7213	Intermediate Similarity	NPC159913
0.7031	Intermediate Similarity	NPC302170
0.6719	Remote Similarity	NPC291957
0.6393	Remote Similarity	NPC31034
0.6061	Remote Similarity	NPC43918
0.6061	Remote Similarity	NPC261411
0.6061	Remote Similarity	NPC190204
0.6027	Remote Similarity	NPC470271
0.597	Remote Similarity	NPC469651
0.5909	Remote Similarity	NPC47521
0.5797	Remote Similarity	NPC311389
0.5694	Remote Similarity	NPC217781
0.5484	Remote Similarity	NPC239019
0.5484	Remote Similarity	NPC247629
0.5385	Remote Similarity	NPC283806
0.5385	Remote Similarity	NPC238419
0.5385	Remote Similarity	NPC129533
0.5385	Remote Similarity	NPC123259
0.5375	Remote Similarity	NPC481310
0.5362	Remote Similarity	NPC14030
0.5333	Remote Similarity	NPC8940
0.5244	Remote Similarity	NPC486113
0.5231	Remote Similarity	NPC205037
0.5231	Remote Similarity	NPC3746
0.5185	Remote Similarity	NPC269625
0.5172	Remote Similarity	NPC483711
0.5156	Remote Similarity	NPC120621
0.5116	Remote Similarity	NPC486112
0.5114	Remote Similarity	NPC65489

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC488888 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5586
0.1-0.2	3540
0.2-0.3	23
0.3-0.4	1
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