NPASS Compound

Natural Product: NPC479934

Natural Product ID	NPC479934
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	ZJFCNRJVXACKKG-PZFKPVGWSA-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]

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 71 73 0 0 0 0 0 0 0 0999 V2000 6.4211 -1.7978 0.8967 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8831 -2.5372 -0.0818 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5513 -2.2321 -0.5670 C 0 0 0 0 0 0 0 0 0 0 0 0 4.0357 -2.9488 -1.5122 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8150 -1.1057 0.0398 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4701 -0.9602 -0.5416 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6006 0.1568 -0.0156 C 0 0 0 0 0 0 0 0 0 0 0 0 2.3477 1.4394 -0.3146 C 0 0 0 0 0 0 0 0 0 0 0 0 1.3562 0.1155 1.4589 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5094 0.5634 2.3160 C 0 0 0 0 0 0 0 0 0 0 0 0 0.1465 0.8726 1.9188 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8994 1.1238 0.9290 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.0329 1.3029 1.3022 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.6667 1.1776 -0.5591 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9222 0.7568 -1.3081 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.2711 -0.4522 -1.5818 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.4641 -1.6700 -1.1924 C 0 0 1 0 0 0 0 0 0 0 0 0 -0.4488 -1.1382 -0.1813 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2857 0.0742 -0.7871 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.3657 -2.5327 -0.5344 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5861 -3.8291 -0.9742 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.9671 -4.2458 -1.9841 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.5267 -4.7567 -0.3030 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5626 -6.0986 -1.0004 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5408 2.0782 -1.6332 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.2097 2.6780 -0.5788 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.5051 3.1114 -0.7352 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1278 2.9848 -1.8213 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.1933 3.7512 0.4184 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3917 2.7572 -2.0513 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5309 2.5276 -0.9693 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.0530 3.3933 0.0659 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.3797 4.5056 0.4948 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7316 4.7985 -0.0185 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9249 5.3928 1.5624 C 0 0 0 0 0 0 0 0 0 0 0 0 5.8989 -0.9755 1.3437 H 0 0 0 0 0 0 0 0 0 0 0 0 7.4082 -2.0279 1.2527 H 0 0 0 0 0 0 0 0 0 0 0 0 6.4325 -3.3490 -0.5038 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5819 -3.7925 -1.9644 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0656 -2.7789 -1.9184 H 0 0 0 0 0 0 0 0 0 0 0 0 4.5097 -0.2484 -0.0640 H 0 0 0 0 0 0 0 0 0 0 0 0 3.7977 -1.3029 1.1513 H 0 0 0 0 0 0 0 0 0 0 0 0 1.9712 -1.9633 -0.4925 H 0 0 0 0 0 0 0 0 0 0 0 0 2.6332 -0.8342 -1.6613 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4402 1.3650 -0.1423 H 0 0 0 0 0 0 0 0 0 0 0 0 2.2986 1.6203 -1.4140 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0251 2.2770 0.3182 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1595 -0.9657 1.7249 H 0 0 0 0 0 0 0 0 0 0 0 0 3.3800 0.9531 1.8012 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7980 -0.2439 3.0551 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1895 1.4060 3.0047 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4380 1.8854 2.3329 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.3253 0.3572 2.7839 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2147 -0.6095 -2.1330 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.9751 -2.1255 -2.0601 H 0 0 0 0 0 0 0 0 0 0 0 0 0.1811 -1.9023 0.2282 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.1115 -0.8217 0.6799 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5188 -0.1498 -1.8376 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.5771 -4.3519 -0.3456 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2862 -4.8953 0.7653 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.6935 -6.7274 -0.7000 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5468 -5.9592 -2.1084 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4928 -6.6522 -0.7677 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.1990 2.0330 -2.5140 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6306 2.9586 1.0585 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9884 4.4107 0.0240 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4635 4.3251 1.0475 H 0 0 0 0 0 0 0 0 0 0 0 0 0.4172 2.9859 -1.2422 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.2258 5.4485 2.4118 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0996 6.3961 1.1185 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8988 4.9988 1.8655 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 3 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 7 9 1 0 9 10 1 0 9 11 1 0 11 12 1 0 12 13 2 0 12 14 1 0 14 15 1 0 15 16 2 0 16 17 1 0 17 18 1 0 18 19 1 0 17 20 1 0 20 21 1 0 21 22 2 0 21 23 1 0 23 24 1 0 15 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 25 30 1 0 30 31 1 0 31 32 1 0 32 33 1 0 33 34 2 0 33 35 1 0 19 7 1 0 19 14 1 0 31 14 1 0 1 36 1 0 1 37 1 0 2 38 1 0 4 39 1 0 4 40 1 0 5 41 1 0 5 42 1 0 6 43 1 0 6 44 1 0 8 45 1 0 8 46 1 0 8 47 1 0 9 48 1 0 10 49 1 0 10 50 1 0 10 51 1 0 11 52 1 0 11 53 1 0 16 54 1 0 17 55 1 6 18 56 1 0 18 57 1 0 19 58 1 0 23 59 1 0 23 60 1 0 24 61 1 0 24 62 1 0 24 63 1 0 25 64 1 6 29 65 1 0 29 66 1 0 29 67 1 0 31 68 1 6 35 69 1 0 35 70 1 0 35 71 1 0 M END

Standard InCHIKey	ZJFCNRJVXACKKG-PZFKPVGWSA-N
Standard InCHI	InChI=1S/C27H36O8/c1-8-15(3)10-11-26(7)16(4)12-22(30)27-20(13-19(14-21(26)27)34-23(31)9-2)24(32-17(5)28)35-25(27)33-18(6)29/h8,13,16,19,21,24-25H,1,3,9-12,14H2,2,4-7H3/t16?,19-,21?,24-,25+,26?,27?/m0/s1
SMILES	C=CC(=C)CCC1(C)C(C)CC(=O)C23C(=C[C@@H](CC12)OC(=O)CC)[C@@H](OC(=O)C)O[C@H]3OC(=O)C

Calculated Properties

Physi-Chem Properties

Molecular Weight:	488.24	Volume:	501.745 ? Van der Waals volume.
Dense:	0.973	LogP:	3.194 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	3.157 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-4.698 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	11.0	Rigid Bonds:	21.0
TPSA:	105.2 ? Topological Polar Surface Area.	H-Bond Acceptor:	8.0
H-Bond Donor:	0.0	Rings:	3.0
Heavy Atoms:	8.0

MedChem Properties

QED Drug-Likeness Score:	0.217	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	5.707	Fsp³:	0.63
MCE-18:	88.636 ? MCE-18 stands for medicinal chemistry evolution.MCE-18≥45 is considered a suitable value.	Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Rejected	GSK Rule:	Accepted
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.371	Fluc inhibitor:	0.002 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.007 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.124 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.339	Promiscuous compounds:	0.482

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-4.784	MDCK Permeability:	-4.693
Pgp-inhibitor:	0.993	Pgp-substrate:	0.231
PAMPA:	0.063 ? 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):	0.003
20% Bioavailability (F20%):	0.842	30% Bioavailability (F30%):	0.992
50% Bioavailability (F50%):	1.0

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.019	MRP1:	0.995
Plasma Protein Binding (PPB):	65.089%	Volume Distribution (VD):	-0.176
Fu:	32.765% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.794
OATP1B3 inhibitor:	0.939	BCRP inhibitor:	0.795
BSEP inhibitor:	1.0

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.234
CYP2C19-inhibitor:	0.44	CYP2C19-substrate:	0.015
CYP2C9-inhibitor:	0.081	CYP2C9-substrate:	0.004
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.014
CYP3A4-inhibitor:	0.012	CYP3A4-substrate:	0.005
CYP2B6-substrate:	0.003	CYP2C8-inhibitor:	0.995
HLM stability:	0.999 ? 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):

6.573

Half-life (T1/2):

0.84

ADMET: Toxicity

hERG Blockers:	0.019	hERG Blockers (10um):	0.205
Human Hepatotoxicity (H-HT):	0.442	Drug-induced Liver Injury (DILI):	0.646
AMES Toxicity:	0.928	Rat Oral Acute Toxicity:	0.774
Maximum Recommended Daily Dose:	0.945	Skin Sensitization:	0.964
Carcinogencity:	0.46	Eye Corrosion:	0.0
Eye Irritation:	0.027	Respiratory Toxicity:	0.185
Drug-induced Neurotoxicity:	0.711	Ototoxicity:	0.475
Hematotoxicity:	0.344	Drug-induced Nephrotoxicity:	0.478
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.163
A549 Cytotoxicity:	0.436	Hek293 Cytotoxicity:	0.357
BCF:	0.755 ? 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:	3.696 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.684 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.954 ? 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
NPO40015	Anacolosa clarkii	Species	Aptandraceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30830773]

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
TGI	4

Activity Type	# Activity
Cell line	2
Others	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
NPT2276	Cell line	A673	Homo sapiens	TGI	=	1100.0	nM	PMID[30830773]
NPT15166	Cell line	Hep293TT	Homo sapiens	TGI	=	1000.0	nM	PMID[30830773]
NPT2	Others	Unspecified	n.a.	TGI	=	520.0	nM	PMID[30830773]
NPT2	Others	Unspecified	n.a.	TGI	=	700.0	nM	PMID[30830773]

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 NPC479934 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	23302
0.1-0.2	24061
0.2-0.3	2354
0.3-0.4	36
0.4-0.5	59
0.5-0.6	27
0.6-0.7	13
0.7-0.8	0
0.8-0.85	1
0.85-0.9	2
0.9-0.95	2
0.95-1	0

Similarity Score	Similarity Level	Natural Product ID
0.9107	High Similarity	NPC479935
0.9107	High Similarity	NPC479936
0.8772	High Similarity	NPC479939
0.8621	High Similarity	NPC479937
0.8475	Intermediate Similarity	NPC479938
0.6615	Remote Similarity	NPC479943
0.6406	Remote Similarity	NPC481018
0.6406	Remote Similarity	NPC171598
0.6212	Remote Similarity	NPC318917
0.6212	Remote Similarity	NPC481019
0.6176	Remote Similarity	NPC479940
0.6176	Remote Similarity	NPC7644
0.6176	Remote Similarity	NPC481017
0.6119	Remote Similarity	NPC488236
0.6029	Remote Similarity	NPC471366
0.6029	Remote Similarity	NPC476800
0.6029	Remote Similarity	NPC488237
0.6	Remote Similarity	NPC472189
0.5882	Remote Similarity	NPC472186
0.5857	Remote Similarity	NPC473545
0.5857	Remote Similarity	NPC475889
0.5857	Remote Similarity	NPC7613
0.5857	Remote Similarity	NPC479942
0.5821	Remote Similarity	NPC481020
0.5797	Remote Similarity	NPC488649
0.5775	Remote Similarity	NPC479941
0.5735	Remote Similarity	NPC471362
0.5735	Remote Similarity	NPC471372
0.5652	Remote Similarity	NPC472188
0.5634	Remote Similarity	NPC217921
0.5634	Remote Similarity	NPC88013
0.5634	Remote Similarity	NPC135015
0.5588	Remote Similarity	NPC132395
0.5588	Remote Similarity	NPC471364
0.5556	Remote Similarity	NPC48548
0.5493	Remote Similarity	NPC128795
0.5479	Remote Similarity	NPC472187
0.5417	Remote Similarity	NPC238397
0.5333	Remote Similarity	NPC127933
0.527	Remote Similarity	NPC488219
0.527	Remote Similarity	NPC471363
0.5224	Remote Similarity	NPC486758
0.5143	Remote Similarity	NPC600724
0.5068	Remote Similarity	NPC471365
0.5062	Remote Similarity	NPC486751

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC479934 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	7554
0.1-0.2	1559
0.2-0.3	37
0.3-0.4	0
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