NPASS Compound

Natural Product: NPC484923

Natural Product ID	NPC484923
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	MUACSCLQRGEGOE-DMIOSSLZSA-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 74 79 0 0 0 0 0 0 0 0999 V2000 5.8735 3.4643 -0.8004 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1306 2.1742 -0.6705 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5723 1.6101 -1.7435 C 0 0 0 0 0 0 0 0 0 0 0 0 3.8454 0.3233 -1.5426 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9147 0.4025 -0.3495 C 0 0 1 0 0 0 0 0 0 0 0 0 3.5865 1.0377 0.8467 C 0 0 0 0 0 0 0 0 0 0 0 0 4.9881 1.4817 0.6185 C 0 0 0 0 0 0 0 0 0 0 0 0 1.7912 1.3082 -0.7640 C 0 0 0 0 0 0 0 0 0 0 0 0 0.5942 1.0848 -0.1470 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.5849 1.7011 -0.4625 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.6663 2.5499 -1.3262 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8014 1.3264 0.2276 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.0325 1.6810 0.0428 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.5901 2.6146 -0.9604 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.6063 1.7754 -1.7534 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.4509 0.4445 -1.4529 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.8160 0.0798 -0.1793 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.4037 -1.3282 0.1453 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1487 -1.7305 -0.0649 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.6270 -3.0444 0.2082 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3864 -3.3780 0.0136 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.3920 -2.4929 -0.4939 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7214 -1.3900 -0.8653 O 0 0 0 0 0 0 0 0 0 0 0 0 0.9688 -2.7833 -0.5882 O 0 0 0 0 0 0 0 0 0 0 0 0 1.8258 -1.7223 -1.0782 C 0 0 2 0 0 0 0 0 0 0 0 0 2.9571 -2.2601 -1.9177 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2344 -1.9304 -1.1736 C 0 0 2 0 0 0 0 0 0 0 0 0 3.7167 -1.8709 0.2455 C 0 0 1 0 0 0 0 0 0 0 0 0 3.8217 -2.9485 1.1032 C 0 0 0 0 0 0 0 0 0 0 0 0 4.5455 -1.7024 1.3179 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4888 -0.9822 0.0479 C 0 0 1 0 0 0 0 0 0 0 0 0 1.7561 -1.0360 1.3607 C 0 0 0 0 0 0 0 0 0 0 0 0 4.7505 -0.6932 -1.4753 O 0 0 0 0 0 0 0 0 0 0 0 0 -6.3167 0.1824 0.0629 C 0 0 2 0 0 0 0 0 0 0 0 0 -6.6822 -0.1860 1.4652 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.9820 -0.6571 -0.8319 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.1299 0.9862 0.8585 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.5203 0.2673 1.8524 O 0 0 0 0 0 0 0 0 0 0 0 0 6.7674 3.4073 -0.1205 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2296 4.3236 -0.5199 H 0 0 0 0 0 0 0 0 0 0 0 0 6.2023 3.6148 -1.8325 H 0 0 0 0 0 0 0 0 0 0 0 0 4.6677 2.1015 -2.7033 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2121 0.1784 -2.4427 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5862 0.3750 1.7467 H 0 0 0 0 0 0 0 0 0 0 0 0 3.0133 1.9457 1.2007 H 0 0 0 0 0 0 0 0 0 0 0 0 5.2323 2.2409 1.4180 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7551 0.6848 0.7500 H 0 0 0 0 0 0 0 0 0 0 0 0 1.6258 1.2003 -1.8767 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1589 2.3668 -0.6611 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.6281 0.6312 1.0436 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.8641 3.0802 -1.6183 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1972 3.3701 -0.3838 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6184 2.1738 -1.5612 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4388 1.9204 -2.8437 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0951 -2.0434 0.5501 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.4851 -1.0454 -0.5090 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.3296 -3.7464 0.5856 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.0578 -4.3662 0.2326 H 0 0 0 0 0 0 0 0 0 0 0 0 1.2118 -1.1055 -1.7354 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9583 -1.8757 -2.9453 H 0 0 0 0 0 0 0 0 0 0 0 0 2.8782 -3.3747 -1.9276 H 0 0 0 0 0 0 0 0 0 0 0 0 5.0165 -2.6934 -1.3058 H 0 0 0 0 0 0 0 0 0 0 0 0 4.4892 -3.8224 0.8547 H 0 0 0 0 0 0 0 0 0 0 0 0 3.1730 -3.1759 1.9656 H 0 0 0 0 0 0 0 0 0 0 0 0 1.0434 -1.8573 1.3536 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4836 -1.2726 2.2023 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3274 -0.0676 1.6886 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6745 1.2157 -0.1130 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.9116 0.1856 2.1998 H 0 0 0 0 0 0 0 0 0 0 0 0 -7.6262 0.3293 1.7434 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.7348 -1.2879 1.6270 H 0 0 0 0 0 0 0 0 0 0 0 0 -6.6271 -0.5985 -1.7482 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8315 1.7577 1.1713 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4151 0.8708 2.6383 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 3 4 1 0 4 5 1 0 5 6 1 1 6 7 1 0 5 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 10 12 1 0 12 13 2 0 13 14 1 0 14 15 1 0 15 16 1 0 17 16 1 6 17 18 1 0 18 19 2 0 19 20 1 0 20 21 2 0 21 22 1 0 22 23 2 0 22 24 1 0 24 25 1 0 25 26 1 0 26 27 1 0 27 28 1 0 28 29 1 0 29 30 1 0 28 31 1 0 31 32 1 1 27 33 1 0 17 34 1 0 34 35 1 0 34 36 1 0 17 37 1 0 37 38 1 0 7 2 1 0 37 13 1 0 33 4 1 0 31 5 1 0 31 25 1 0 28 30 1 1 1 39 1 0 1 40 1 0 1 41 1 0 3 42 1 0 4 43 1 6 6 44 1 0 6 45 1 0 7 46 1 0 7 47 1 0 8 48 1 0 8 49 1 0 12 50 1 0 14 51 1 0 14 52 1 0 15 53 1 0 15 54 1 0 18 55 1 0 19 56 1 0 20 57 1 0 21 58 1 0 25 59 1 6 26 60 1 0 26 61 1 0 27 62 1 1 29 63 1 0 29 64 1 0 32 65 1 0 32 66 1 0 32 67 1 0 34 68 1 6 35 69 1 0 35 70 1 0 35 71 1 0 36 72 1 0 37 73 1 1 38 74 1 0 M END

Standard InCHIKey	MUACSCLQRGEGOE-DMIOSSLZSA-N
Standard InCHI	InChI=1S/C29H36O9/c1-17-7-10-27-15-34-24(32)13-19-8-11-35-28(18(2)30,25(19)33)9-5-4-6-23(31)38-20-14-22(37-21(27)12-17)29(16-36-29)26(20,27)3/h4-6,9,12-13,18,20-22,25,30,33H,7-8,10-11,14-16H2,1-3H3/b6-4-,9-5+,19-13+/t18-,20+,21+,22+,25-,26+,27+,28+,29+/m0/s1
SMILES	CC1=C[C@@H]2[C@@]3(CC1)COC(=O)/C=C/1CCO[C@](/C=C/C=CC(=O)O[C@@H]4C[C@H]([C@]5(CO5)[C@@]34C)O2)([C@H](C)O)[C@H]1O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	528.24	Volume:	522.095 ? Van der Waals volume.
Dense:	1.012	LogP:	1.014 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.471 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.116 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	1.0	Rigid Bonds:	37.0
TPSA:	124.05 ? Topological Polar Surface Area.	H-Bond Acceptor:	9.0
H-Bond Donor:	2.0	Rings:	6.0
Heavy Atoms:	9.0

MedChem Properties

QED Drug-Likeness Score:	0.299	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	7.777	Fsp³:	0.655
MCE-18:	141.375 ? 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:	Accepted	BMS Rule:	1
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.678	Fluc inhibitor:	0.095 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.092 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.1 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.135	Promiscuous compounds:	0.372

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.359	MDCK Permeability:	-5.008
Pgp-inhibitor:	0.001	Pgp-substrate:	0.604
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):	0.014
20% Bioavailability (F20%):	0.881	30% Bioavailability (F30%):	0.704
50% Bioavailability (F50%):	0.988

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.133	MRP1:	0.802
Plasma Protein Binding (PPB):	68.176%	Volume Distribution (VD):	-0.151
Fu:	25.29% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.946
OATP1B3 inhibitor:	0.524	BCRP inhibitor:	0.007
BSEP inhibitor:	0.874

ADMET: Metabolism

CYP1A2-inhibitor:	0.285	CYP1A2-substrate:	0.008
CYP2C19-inhibitor:	0.924	CYP2C19-substrate:	0.02
CYP2C9-inhibitor:	0.607	CYP2C9-substrate:	0.057
CYP2D6-inhibitor:	0.072	CYP2D6-substrate:	0.071
CYP3A4-inhibitor:	0.0	CYP3A4-substrate:	0.848
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.49
HLM stability:	0.887 ? 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):

5.569

Half-life (T1/2):

2.433

ADMET: Toxicity

hERG Blockers:	0.008	hERG Blockers (10um):	0.121
Human Hepatotoxicity (H-HT):	0.96	Drug-induced Liver Injury (DILI):	0.978
AMES Toxicity:	0.999	Rat Oral Acute Toxicity:	0.979
Maximum Recommended Daily Dose:	0.999	Skin Sensitization:	1.0
Carcinogencity:	0.771	Eye Corrosion:	0.0
Eye Irritation:	0.068	Respiratory Toxicity:	0.964
Drug-induced Neurotoxicity:	0.98	Ototoxicity:	0.758
Hematotoxicity:	0.514	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.958
A549 Cytotoxicity:	0.991	Hek293 Cytotoxicity:	0.989
BCF:	0.709 ? 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:	3.551 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.452 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	4.625 ? 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
NPO7578	Trichoderma cornu-damae	Species	Hypocreaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[30457333]
NPO7578	Trichoderma cornu-damae	Species	Hypocreaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO7578	Trichoderma cornu-damae	Species	Hypocreaceae	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
IC50	4

Activity Type	# Activity
Cell line	4

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
NPT457	Cell line	BT-549	Homo sapiens	IC50	=	0.3	nM	PMID[30457333]
NPT2459	Cell line	HCC70	Homo sapiens	IC50	=	1.0	nM	PMID[30457333]
NPT82	Cell line	MDA-MB-231	Homo sapiens	IC50	=	0.4	nM	PMID[30457333]
NPT784	Cell line	MDA-MB-468	Homo sapiens	IC50	=	3.0	nM	PMID[30457333]

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 NPC484923 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	17791
0.1-0.2	30967
0.2-0.3	1033
0.3-0.4	23
0.4-0.5	12
0.5-0.6	8
0.6-0.7	16
0.7-0.8	0
0.8-0.85	0
0.85-0.9	0
0.9-0.95	0
0.95-1	1

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC484922
0.7531	Intermediate Similarity	NPC484155
0.7317	Intermediate Similarity	NPC474286
0.7317	Intermediate Similarity	NPC484150
0.7067	Intermediate Similarity	NPC98813
0.7067	Intermediate Similarity	NPC600365
0.7059	Intermediate Similarity	NPC475130
0.7059	Intermediate Similarity	NPC484151
0.6914	Remote Similarity	NPC29389
0.6914	Remote Similarity	NPC112316
0.6667	Remote Similarity	NPC469959
0.6667	Remote Similarity	NPC469957
0.6628	Remote Similarity	NPC484144
0.6588	Remote Similarity	NPC484149
0.6582	Remote Similarity	NPC484152
0.6429	Remote Similarity	NPC472263
0.6386	Remote Similarity	NPC13743
0.6265	Remote Similarity	NPC98038
0.6265	Remote Similarity	NPC313921
0.6235	Remote Similarity	NPC108682
0.6222	Remote Similarity	NPC484153
0.6222	Remote Similarity	NPC484925
0.6111	Remote Similarity	NPC484145
0.6067	Remote Similarity	NPC484921
0.5914	Remote Similarity	NPC484154
0.5843	Remote Similarity	NPC101965
0.5843	Remote Similarity	NPC101400
0.5632	Remote Similarity	NPC9579
0.5476	Remote Similarity	NPC265502
0.5275	Remote Similarity	NPC484924
0.5111	Remote Similarity	NPC469960
0.5111	Remote Similarity	NPC93026

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC484923 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	6884
0.1-0.2	2259
0.2-0.3	7
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