NPASS Compound

Natural Product: NPC149945

Natural Product ID	NPC149945
Common Name ? The InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.	Cipatrijugin B
IUPAC Name	n.a.
Synonyms
Synthetic Gene Cluster	n.a.
ChEMBL Identifier	CHEMBL400181
PubChem CID	23626011
Chemical Classification	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000264] Organic acids and derivatives [CHEMONTID:0000265] Carboxylic acids and derivatives [CHEMONTID:0001986] Tricarboxylic acids and derivatives

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 75 79 0 0 0 0 0 0 0 0999 V2000 -1.3576 2.3952 1.9968 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.3565 1.7347 0.8681 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8703 2.1123 -0.4835 C 0 0 2 0 0 0 0 0 0 0 0 0 -1.9622 1.5310 -1.4191 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.8485 0.7130 -0.5160 C 0 0 1 0 0 0 0 0 0 0 0 0 -3.9607 1.6178 -0.0692 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.3212 -0.5652 -1.1193 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.7718 -0.4612 -1.4163 C 0 0 0 0 0 0 0 0 0 0 0 0 -5.8397 -0.5062 -0.5185 C 0 0 0 0 0 0 0 0 0 0 0 0 -7.0159 -0.3692 -1.2336 C 0 0 0 0 0 0 0 0 0 0 0 0 -6.6942 -0.2472 -2.4951 O 0 0 0 0 0 0 0 0 0 0 0 0 -5.3862 -0.2953 -2.6516 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.1963 -1.6393 -0.1722 O 0 0 0 0 0 0 0 0 0 0 0 0 -3.3097 -1.4366 1.1975 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.9921 -2.2203 1.8947 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5828 -0.2574 1.7540 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.8769 0.3722 0.5963 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.9218 -0.4412 0.0318 O 0 0 0 0 0 0 0 0 0 0 0 0 0.3019 -0.4699 0.7077 C 0 0 1 0 0 0 0 0 0 0 0 0 0.7453 -1.8933 0.6210 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2196 -2.0583 0.8660 C 0 0 2 0 0 0 0 0 0 0 0 0 3.0509 -1.2483 -0.0515 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3385 -2.1563 -1.2632 C 0 0 0 0 0 0 0 0 0 0 0 0 4.3950 -1.0358 0.5930 C 0 0 0 0 0 0 0 0 0 0 0 0 2.4217 0.0006 -0.6184 C 0 0 2 0 0 0 0 0 0 0 0 0 3.5626 0.9527 -0.8164 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3263 2.2579 -1.3974 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4677 2.4372 -2.6579 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9496 3.3657 -0.6791 O 0 0 0 0 0 0 0 0 0 0 0 0 2.7196 4.6447 -1.2438 C 0 0 0 0 0 0 0 0 0 0 0 0 1.2908 0.5469 0.1476 C 0 0 2 0 0 0 0 0 0 0 0 0 1.6698 1.4236 1.3300 C 0 0 0 0 0 0 0 0 0 0 0 0 0.4093 1.3788 -0.7425 C 0 0 0 0 0 0 0 0 0 0 0 0 0.7661 1.4947 -1.8822 O 0 0 0 0 0 0 0 0 0 0 0 0 2.4847 -3.4639 0.7325 O 0 0 0 0 0 0 0 0 0 0 0 0 2.8636 -4.2540 1.7972 C 0 0 0 0 0 0 0 0 0 0 0 0 2.9763 -3.7076 2.9192 O 0 0 0 0 0 0 0 0 0 0 0 0 3.1103 -5.6907 1.5398 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.7705 3.4631 -0.6861 O 0 0 0 0 0 0 0 0 0 0 0 0 -0.9643 3.3992 2.0927 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.7660 1.9338 2.8866 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.4616 0.8631 -2.1190 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.5090 2.3622 -1.9088 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.5901 2.6828 0.0080 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.7084 1.6482 -0.8882 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.4659 1.3420 0.8504 H 0 0 0 0 0 0 0 0 0 0 0 0 -2.7748 -0.8659 -2.0253 H 0 0 0 0 0 0 0 0 0 0 0 0 -5.7892 -0.6250 0.5346 H 0 0 0 0 0 0 0 0 0 0 0 0 -8.0112 -0.3671 -0.7998 H 0 0 0 0 0 0 0 0 0 0 0 0 -4.8660 -0.2175 -3.5992 H 0 0 0 0 0 0 0 0 0 0 0 0 -1.8254 -0.6161 2.4784 H 0 0 0 0 0 0 0 0 0 0 0 0 -3.2611 0.4485 2.2195 H 0 0 0 0 0 0 0 0 0 0 0 0 0.0524 -0.2678 1.7691 H 0 0 0 0 0 0 0 0 0 0 0 0 0.5158 -2.2743 -0.3906 H 0 0 0 0 0 0 0 0 0 0 0 0 0.2170 -2.4819 1.3981 H 0 0 0 0 0 0 0 0 0 0 0 0 2.3881 -1.8139 1.9468 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1198 -2.8847 -1.0408 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4071 -2.6907 -1.5070 H 0 0 0 0 0 0 0 0 0 0 0 0 3.5704 -1.5016 -2.1431 H 0 0 0 0 0 0 0 0 0 0 0 0 4.8167 -2.0217 0.9615 H 0 0 0 0 0 0 0 0 0 0 0 0 5.1711 -0.6347 -0.0513 H 0 0 0 0 0 0 0 0 0 0 0 0 4.3517 -0.4207 1.5142 H 0 0 0 0 0 0 0 0 0 0 0 0 2.0280 -0.2226 -1.6497 H 0 0 0 0 0 0 0 0 0 0 0 0 4.1083 1.0636 0.1651 H 0 0 0 0 0 0 0 0 0 0 0 0 4.2860 0.4321 -1.5440 H 0 0 0 0 0 0 0 0 0 0 0 0 1.8951 4.6086 -1.9751 H 0 0 0 0 0 0 0 0 0 0 0 0 3.6378 5.0561 -1.7359 H 0 0 0 0 0 0 0 0 0 0 0 0 2.4857 5.3379 -0.4119 H 0 0 0 0 0 0 0 0 0 0 0 0 1.1898 1.0429 2.2883 H 0 0 0 0 0 0 0 0 0 0 0 0 2.7565 1.3579 1.5872 H 0 0 0 0 0 0 0 0 0 0 0 0 1.3546 2.4655 1.2298 H 0 0 0 0 0 0 0 0 0 0 0 0 3.8220 -5.7796 0.6952 H 0 0 0 0 0 0 0 0 0 0 0 0 2.1407 -6.1046 1.1440 H 0 0 0 0 0 0 0 0 0 0 0 0 3.4525 -6.2477 2.4188 H 0 0 0 0 0 0 0 0 0 0 0 0 -0.8090 3.9691 0.1410 H 0 0 0 0 0 0 0 0 0 0 0 0 1 2 2 0 2 3 1 0 3 4 1 0 4 5 1 0 5 6 1 1 5 7 1 0 7 8 1 0 8 9 1 0 9 10 2 0 10 11 1 0 11 12 1 0 7 13 1 0 13 14 1 0 14 15 2 0 14 16 1 0 16 17 1 0 17 18 1 6 18 19 1 0 19 20 1 0 20 21 1 0 21 22 1 0 22 23 1 0 22 24 1 0 22 25 1 0 25 26 1 0 26 27 1 0 27 28 2 0 27 29 1 0 29 30 1 0 25 31 1 0 31 32 1 1 31 33 1 0 33 34 2 0 21 35 1 0 35 36 1 0 36 37 2 0 36 38 1 0 3 39 1 1 17 2 1 0 31 19 1 0 33 3 1 0 17 5 1 0 12 8 2 0 1 40 1 0 1 41 1 0 4 42 1 0 4 43 1 0 6 44 1 0 6 45 1 0 6 46 1 0 7 47 1 6 9 48 1 0 10 49 1 0 12 50 1 0 16 51 1 0 16 52 1 0 19 53 1 1 20 54 1 0 20 55 1 0 21 56 1 1 23 57 1 0 23 58 1 0 23 59 1 0 24 60 1 0 24 61 1 0 24 62 1 0 25 63 1 6 26 64 1 0 26 65 1 0 30 66 1 0 30 67 1 0 30 68 1 0 32 69 1 0 32 70 1 0 32 71 1 0 38 72 1 0 38 73 1 0 38 74 1 0 39 75 1 0 M END

Standard InCHIKey	GOEQVXYKRUHLMM-IZZXIUOXSA-N
Standard InCHI	InChI=1S/C29H36O10/c1-15-28(34)14-26(5)23(17-8-9-36-13-17)38-22(32)12-29(15,26)39-20-11-19(37-16(2)30)25(3,4)18(10-21(31)35-7)27(20,6)24(28)33/h8-9,13,18-20,23,34H,1,10-12,14H2,2-7H3/t18-,19+,20-,23-,26-,27+,28+,29-/m0/s1
SMILES	C=C1[C@@]2(C[C@@]3(C)[C@H](c4ccoc4)OC(=O)C[C@]13O[C@H]1C[C@H](C(C)(C)[C@H](CC(=O)OC)[C@@]1(C)C2=O)OC(=O)C)O

Calculated Properties

Physi-Chem Properties

Molecular Weight:	544.23	Volume:	536.805 ? Van der Waals volume.
Dense:	1.014	LogP:	1.194 ? The logarithm of the n-octanol/water distribution coefficients.
logD7.4:	1.692 ? The logarithm of the n-octanol/water distribution coefficient at pH=7.4.	LogS:	-3.23 ? The logarithm of aqueous solubility value.
Rotatable Bonds:	6.0	Rigid Bonds:	30.0
TPSA:	138.57 ? Topological Polar Surface Area.	H-Bond Acceptor:	10.0
H-Bond Donor:	1.0	Rings:	5.0
Heavy Atoms:	10.0

MedChem Properties

QED Drug-Likeness Score:	0.341	GASA:	1.0 ? GASA represents the probability of being difficult to synthesize, ranging from 0 to 1.
Synthetic Accessibility Score:	6.463	Fsp³:	0.655
MCE-18:	180.0 ? 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:	0
Chelating Alert:	0	PAINS Alert:	0
Colloidal aggregators:	0.263	Fluc inhibitor:	0.0 ? The fluc inhibitor value is the probability of being fLuc inhibitors, within the range of 0 to 1.
Blue fluorescence:	0.006 ? The blue fluorescence value is the probability of being blue fluorescence, within the range of 0 to 1	Green fluorescence:	0.025 ? The green fluorescence value is the probability of being green fluorescence, within the range of 0 to 1
Reactive compounds:	0.068	Promiscuous compounds:	0.439

ADMET Properties (ADMETlab3.0)

ADMET: Absorption

Caco-2 Permeability:	-5.161	MDCK Permeability:	-4.989
Pgp-inhibitor:	0.874	Pgp-substrate:	0.484
PAMPA:	0.941 ? 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):	0.011
20% Bioavailability (F20%):	0.073	30% Bioavailability (F30%):	0.435
50% Bioavailability (F50%):	0.798

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.0	MRP1:	0.984
Plasma Protein Binding (PPB):	59.849%	Volume Distribution (VD):	-0.29
Fu:	39.699% ? The fraction unbound in plasms.	OATP1B1 inhibitor:	0.986
OATP1B3 inhibitor:	0.725	BCRP inhibitor:	0.094
BSEP inhibitor:	0.857

ADMET: Metabolism

CYP1A2-inhibitor:	0.097	CYP1A2-substrate:	0.01
CYP2C19-inhibitor:	0.955	CYP2C19-substrate:	0.01
CYP2C9-inhibitor:	0.005	CYP2C9-substrate:	0.0
CYP2D6-inhibitor:	0.0	CYP2D6-substrate:	0.575
CYP3A4-inhibitor:	0.593	CYP3A4-substrate:	0.064
CYP2B6-substrate:	0.033	CYP2C8-inhibitor:	0.998
HLM stability:	0.891 ? 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):

5.711

Half-life (T1/2):

1.525

ADMET: Toxicity

hERG Blockers:	0.012	hERG Blockers (10um):	0.037
Human Hepatotoxicity (H-HT):	0.821	Drug-induced Liver Injury (DILI):	0.964
AMES Toxicity:	0.807	Rat Oral Acute Toxicity:	0.917
Maximum Recommended Daily Dose:	0.932	Skin Sensitization:	0.997
Carcinogencity:	0.986	Eye Corrosion:	0.001
Eye Irritation:	0.46	Respiratory Toxicity:	0.1
Drug-induced Neurotoxicity:	0.525	Ototoxicity:	0.345
Hematotoxicity:	0.508	Drug-induced Nephrotoxicity:	0.998
Genotoxicity:	1.0	RPMI-8226 Immunitoxicity:	0.222
A549 Cytotoxicity:	0.439	Hek293 Cytotoxicity:	0.158
BCF:	0.492 ? 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:	3.346 ? 48 hour Tetrahymena pyriformis IGC50. The unit of IGC50 is -log10[(mg/L)/(1000*MW)].
LC50DM:	5.704 ? 48 hour Daphnia magna LC50. The unit of LC50DM is -log10[(mg/L)/(1000*MW)].	LC50FM:	5.066 ? 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
NPO4584	Cipadessa cinerascens	Species	Meliaceae	Eukaryota	leaves	n.a.	n.a.	PMID[17655260]
NPO4584	Cipadessa cinerascens	Species	Meliaceae	Eukaryota	Leaves	n.a.	n.a.	PMID[19296669]
NPO4584	Cipadessa cinerascens	Species	Meliaceae	Eukaryota	leaves	Longlin County of Guangxi Province, China	2012-JUL	PMID[25970729]
NPO4584	Cipadessa cinerascens	Species	Meliaceae	Eukaryota	n.a.	n.a.	n.a.	Database[COCONUT]
NPO4584	Cipadessa cinerascens	Species	Meliaceae	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
ED50	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
NPT81	Cell line	A549	Homo sapiens	ED50	>	5.0	ug ml-1	PMID[22769561]
NPT111	Cell line	K562	Homo sapiens	ED50	>	5.0	ug ml-1	PMID[23327668]

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 NPC149945 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	9910
0.1-0.2	37963
0.2-0.3	1741
0.3-0.4	186
0.4-0.5	41
0.5-0.6	10
0.6-0.7	4
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
0.7108	Intermediate Similarity	NPC249021
0.7073	Intermediate Similarity	NPC282445
0.6951	Remote Similarity	NPC204663
0.6786	Remote Similarity	NPC6326
0.6548	Remote Similarity	NPC195131
0.6506	Remote Similarity	NPC476122
0.573	Remote Similarity	NPC472772
0.5714	Remote Similarity	NPC82851
0.5604	Remote Similarity	NPC200782
0.5444	Remote Similarity	NPC472767
0.5444	Remote Similarity	NPC472765
0.5326	Remote Similarity	NPC472764
0.5326	Remote Similarity	NPC476224
0.5275	Remote Similarity	NPC476262
0.5269	Remote Similarity	NPC472766
0.5111	Remote Similarity	NPC196864

Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC149945 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.5 or Top200).

range	Tanimoto Coefficient
0-0.1	3416
0.1-0.2	5685
0.2-0.3	49
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