NPASS Compound

Natural Product: NPC509862

Natural Product ID	NPC509862
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	7-Acetylintermedine
IUPAC Name	[(7~{R},8~{R})-7-acetoxy-5,6,7,8-tetrahydro-3~{H}-pyrrolizin-1-yl]methyl (2~{S})-2-hydroxy-2-[(1~{R})-1-hydroxyethyl]-3-methyl-butanoate
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 51 52 0 0 0 0 0 0 0 0999 V2000 3.7627 2.0991 1.7507 C 0 0 0 0 0 0 0 0 0 0 0 0 3.6686 0.6594 1.3921 C 0 0 0 0 0 0 0 0 0 0 0 0 3.5754 -0.1656 2.3377 O 0 0 0 0 0 0 0 0 0 0 0 0 3.6770 0.1810 0.1074 O 0 0 0 0 0 0 0 0 0 0 0 0 3.5852 -1.2099 -0.2112 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8145 -1.5295 -1.0450 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4224 -0.8268 -2.3509 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9893 -0.9000 -2.4287 N 0 0 0 0 0 0 0 0 0 0 0 0 2.3421 0.3803 -2.5053 C 0 0 0 0 0 0 0 0 0 0 0 0 1.1306 0.2701 -1.6463 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2202 -0.8214 -0.8810 C 0 0 0 0 0 0 0 0 0 0 0 0 0.2580 -1.3349 0.1224 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8815 -0.5408 0.2538 O 0 0 0 0 0 0 0 0 0 0 0 0 -1.8725 -0.8801 1.1444 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.7041 -1.9255 1.8244 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.1110 -0.0763 1.3321 C 0 0 2 0 0 0 0 0 0 0 0 0 -3.9094 -0.6819 2.3000 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.8979 -0.1087 0.0297 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.1686 0.6782 0.1240 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.2719 -1.5500 -0.2580 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8196 1.3201 1.7923 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.9028 2.0661 0.8557 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.0238 1.9955 1.9340 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4953 -1.4642 -1.2132 C 0 0 2 0 0 0 0 0 0 0 0 0 4.8412 2.3108 1.9896 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5164 2.7559 0.8935 H 0 0 0 0 0 0 0 0 0 0 0 0 3.2036 2.3503 2.6653 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5088 -1.8276 0.6913 H 0 0 0 0 0 0 0 0 0 0 0 0 5.7389 -1.1423 -0.6233 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8283 -2.6333 -1.2348 H 0 0 0 0 0 0 0 0 0 0 0 0 4.9540 -1.2215 -3.2134 H 0 0 0 0 0 0 0 0 0 0 0 0 4.7232 0.2488 -2.1935 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0532 0.5403 -3.5698 H 0 0 0 0 0 0 0 0 0 0 0 0 2.9886 1.2134 -2.2209 H 0 0 0 0 0 0 0 0 0 0 0 0 0.3182 0.9772 -1.6587 H 0 0 0 0 0 0 0 0 0 0 0 0 0.7981 -1.4262 1.1003 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.0539 -2.3729 -0.1480 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.6841 -0.3686 3.2101 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2553 0.2156 -0.8260 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.6222 0.5035 1.1099 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.8740 0.2410 -0.6354 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.0604 1.7456 -0.1450 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.4353 -2.1303 -0.6740 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.6423 -1.9931 0.6988 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.1663 -1.5228 -0.9270 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.3454 1.2692 2.7723 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7847 1.5814 -0.1254 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.2801 3.0999 0.6936 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8864 2.1796 1.2879 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.1601 2.3363 2.8583 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3998 -2.5644 -1.3238 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 1 0 2 3 2 0 2 4 1 0 4 5 1 0 5 6 1 0 6 7 1 0 7 8 1 0 8 9 1 0 9 10 1 0 10 11 2 0 11 12 1 0 12 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 1 16 18 1 0 18 19 1 0 18 20 1 0 16 21 1 0 21 22 1 0 21 23 1 0 11 24 1 0 24 5 1 0 24 8 1 0 1 25 1 0 1 26 1 0 1 27 1 0 5 28 1 1 6 29 1 0 6 30 1 0 7 31 1 0 7 32 1 0 9 33 1 0 9 34 1 0 10 35 1 0 12 36 1 0 12 37 1 0 17 38 1 0 18 39 1 0 19 40 1 0 19 41 1 0 19 42 1 0 20 43 1 0 20 44 1 0 20 45 1 0 21 46 1 1 22 47 1 0 22 48 1 0 22 49 1 0 23 50 1 0 24 51 1 6 M END

Standard InCHIKey	RKDOFSJTBIDAHX-CYHLAULCSA-N
Standard InCHI	InChI=1S/C17H27NO6/c1-10(2)17(22,11(3)19)16(21)23-9-13-5-7-18-8-6-14(15(13)18)24-12(4)20/h5,10-11,14-15,19,22H,6-9H2,1-4H3/t11-,14-,15-,17+/m1/s1
SMILES	CC(=O)O[C@@H]1CCN2CC=C(COC(=O)[C@](O)(C(C)C)[C@@H](C)O)[C@H]12

Calculated Properties

Physi-Chem Properties

Molecular Weight:	341.18	Volume:	341.304 ? Van der Waals volume.
Dense:	1.0	LogP:	1.402 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.591 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-2.012 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	8.0	Rigid Bonds:	11.0
TPSA:	96.3 ? Topological Polar Surface Area.	H-Bond Acceptor:	7.0
H-Bond Donor:	2.0	Rings:	2.0
Heavy Atoms:	7.0

MedChem Properties

QED Drug-Likeness Score:	0.528	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	4.294	Fsp³:	0.765
MCE-18:	39.667 ? 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:	Rejected
Golden Triangle Rule:	Rejected	BMS Rule:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.294	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.026 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.002 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.006	Promiscuous compounds:	0.336

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.302	MDCK Permeability:	-5.008
Pgp-inhibitor:	0.076	Pgp-substrate:	0.331
PAMPA:	0.562 ? 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):	0.039
20% Bioavailability (F20%):	0.884	30% Bioavailability (F30%):	0.984
50% Bioavailability (F50%):	0.997

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.001	MRP1:	0.99
Plasma Protein Binding (PPB):	48.179%	Volume Distribution (VD):	0.054
Fu:	48.788% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.999
OATP1B3 inhibitor:	0.996	BCRP inhibitor:	0.01
BSEP inhibitor:	0.914

ADMET: Metabolism

CYP1A2-inhibitor:	0.001	CYP1A2-substrate:	0.016
CYP2C19-inhibitor:	0.0	CYP2C19-substrate:	0.052
CYP2C9-inhibitor:	0.001	CYP2C9-substrate:	0.014
CYP2D6-inhibitor:	0.001	CYP2D6-substrate:	0.004
CYP3A4-inhibitor:	0.001	CYP3A4-substrate:	0.277
CYP2B6-substrate:	0.0	CYP2C8-inhibitor:	0.917
HLM stability:	0.753 ? 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):

8.214

Half-life (T1/2):

2.253

ADMET: Toxicity

hERG Blockers:	0.072	hERG Blockers (10um):	0.283
Human Hepatotoxicity (H-HT):	0.904	Drug-induced Liver Injury (DILI):	0.197
AMES Toxicity:	0.563	Rat Oral Acute Toxicity:	0.488
Maximum Recommended Daily Dose:	0.644	Skin Sensitization:	0.988
Carcinogencity:	0.98	Eye Corrosion:	0.0
Eye Irritation:	0.093	Respiratory Toxicity:	0.505
Drug-induced Neurotoxicity:	0.257	Ototoxicity:	0.43
Hematotoxicity:	0.291	Drug-induced Nephrotoxicity:	0.495
Genotoxicity:	0.996	RPMI-8226 Immunitoxicity:	0.106
A549 Cytotoxicity:	0.072	Hek293 Cytotoxicity:	0.421
BCF:	0.465 ? 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:	3.23 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	4.746 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	3.952 ? 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
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[38797382]
NPO23959	Echium humile	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO48061	Symphytum x.uplandicum	Genus	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO63033	Lappula spinocarpos	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO47550	Symphytum tuberosum L.	Genus	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO44484	Symphytum bulbosum K. F. Schimp.	Genus	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO50460	Borago officinalis L.	Genus	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO26680	Amsinckia intermedia	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO15142	Echium plantagineum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Seed Essent. Oil	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota		n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Shoot	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Seed Oil	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Seed	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Root	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Plant	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Leaf	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	Fruit Essent. Oil	n.a.	n.a.	Database[FooDB]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15142	Echium plantagineum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO15142	Echium plantagineum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO19080	Borago officinalis	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO23959	Echium humile	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO15142	Echium plantagineum	Species	Boraginaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO26680	Amsinckia intermedia	Species	Boraginaceae	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 NPC509862 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	17227
0.1-0.2	30243
0.2-0.3	2352
0.3-0.4	10
0.4-0.5	4
0.5-0.6	3
0.6-0.7	18
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
0.7288	Intermediate Similarity	NPC608959
0.7241	Intermediate Similarity	NPC608751
0.6897	Remote Similarity	NPC30911
0.6897	Remote Similarity	NPC608092
0.678	Remote Similarity	NPC130124
0.678	Remote Similarity	NPC193471
0.678	Remote Similarity	NPC608663
0.6721	Remote Similarity	NPC316984
0.6721	Remote Similarity	NPC23963
0.6557	Remote Similarity	NPC47857
0.6557	Remote Similarity	NPC181510
0.6557	Remote Similarity	NPC168758
0.6557	Remote Similarity	NPC602310
0.6557	Remote Similarity	NPC609037
0.6452	Remote Similarity	NPC201889
0.6452	Remote Similarity	NPC106791
0.6452	Remote Similarity	NPC607716
0.625	Remote Similarity	NPC279833
0.625	Remote Similarity	NPC173690
0.625	Remote Similarity	NPC80439
0.5469	Remote Similarity	NPC610562
0.5441	Remote Similarity	NPC600980
0.5079	Remote Similarity	NPC64168

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC509862 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	5314
0.1-0.2	3758
0.2-0.3	75
0.3-0.4	2
0.4-0.5	0
0.5-0.6	0
0.6-0.7	1
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
0.6897	Remote Similarity	NPD2204	Approved

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