NPASS Compound

Structure

CID111323 OpenBabel06191715462D 37 40 0 0 1 0 0 0 0 0999 V2000 5.0858 -3.1738 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.1814 -2.8806 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2974 3.8398 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -4.1512 3.3467 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0006 1.9374 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.0003 -0.9863 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.5027 0.4573 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.0231 -2.3562 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6493 2.8540 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8249 2.3784 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.3211 -1.7361 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2510 -1.5378 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2966 0.9502 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6470 0.9516 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.8241 -0.4761 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4733 2.3779 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4731 1.4263 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.1204 1.4258 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 1.6473 0.0005 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.8246 1.4267 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 2.6846 -1.0299 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.6484 -0.0005 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8244 -0.4756 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -4.1206 2.3775 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.8876 -2.2440 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -3.2971 2.8536 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0003 0.9511 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.0000 -0.0000 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 -1.6487 0.9506 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 0.8249 -1.4263 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -4.9744 0.9324 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.5017 -0.4922 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 2.9778 -0.1255 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.5024 -0.4938 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -4.9663 2.8652 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 5.8174 -2.0458 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.1188 -2.0629 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 25 1 0 0 0 0 2 25 1 0 0 0 0 3 26 1 0 0 0 0 4 26 1 0 0 0 0 5 27 1 0 0 0 0 9 10 1 0 0 0 0 9 16 2 0 0 0 0 10 20 1 0 0 0 0 11 12 2 0 0 0 0 11 21 1 0 0 0 0 12 25 1 0 0 0 0 13 17 1 0 0 0 0 13 18 2 0 0 0 0 14 19 1 0 0 0 0 14 27 1 0 0 0 0 15 22 1 0 0 0 0 15 28 1 0 0 0 0 16 17 1 0 0 0 0 16 26 1 0 0 0 0 17 29 1 6 0 0 0 18 24 1 0 0 0 0 18 31 1 0 0 0 0 19 23 1 0 0 0 0 19 32 1 1 0 0 0 20 27 1 1 0 0 0 20 29 1 0 0 0 0 21 30 1 0 0 0 0 21 33 2 0 0 0 0 22 29 1 0 0 0 0 22 34 2 0 0 0 0 23 28 1 6 0 0 0 23 30 1 0 0 0 0 24 26 1 0 0 0 0 24 35 2 0 0 0 0 25 36 1 0 0 0 0 27 28 1 1 0 0 0 28 6 1 6 0 0 0 29 7 1 6 0 0 0 30 8 1 1 0 0 0 30 37 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	514.29
Volume:	538.923
LogP:	2.142
LogD:	2.344
LogS:	-4.395
# Rotatable Bonds:	4
TPSA:	128.97
# H-Bond Aceptor:	7
# H-Bond Donor:	3
# Rings:	4
# Heavy Atoms:	7

MedChem Properties

QED Drug-Likeness Score:	0.299
Synthetic Accessibility Score:	5.526
Fsp3:	0.733
Lipinski Rule-of-5:	Accepted
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	1

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.024
MDCK Permeability:	2.493041210982483e-05
Pgp-inhibitor:	0.989
Pgp-substrate:	0.01
Human Intestinal Absorption (HIA):	0.032
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.004

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.969
Plasma Protein Binding (PPB):	63.91881561279297%
Volume Distribution (VD):	0.407
Pgp-substrate:	22.60041618347168%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.681
CYP2C19-inhibitor:	0.044
CYP2C19-substrate:	0.788
CYP2C9-inhibitor:	0.068
CYP2C9-substrate:	0.229
CYP2D6-inhibitor:	0.007
CYP2D6-substrate:	0.077
CYP3A4-inhibitor:	0.854
CYP3A4-substrate:	0.675

ADMET: Excretion

Clearance (CL):	4.11
Half-life (T1/2):	0.235

ADMET: Toxicity

hERG Blockers:	0.01
Human Hepatotoxicity (H-HT):	0.177
Drug-inuced Liver Injury (DILI):	0.086
AMES Toxicity:	0.055
Rat Oral Acute Toxicity:	0.476
Maximum Recommended Daily Dose:	0.439
Skin Sensitization:	0.245
Carcinogencity:	0.756
Eye Corrosion:	0.005
Eye Irritation:	0.016
Respiratory Toxicity:	0.885

Download Data

Data Type	Select
General Info & Identifiers & Properties
Structure MOL file
Source Organisms
Biological Activities
Similar NPs/Drugs

Natural Product: NPC111323

Natural Product ID:	NPC111323
*Common Name:**	Cucurbitacin I
IUPAC Name:	(8S,9R,10R,13R,14S,16R,17R)-17-[(E,2R)-2,6-dihydroxy-6-methyl-3-oxohept-4-en-2-yl]-2,16-dihydroxy-4,4,9,13,14-pentamethyl-8,10,12,15,16,17-hexahydro-7H-cyclopenta[a]phenanthrene-3,11-dione
Synonyms:	NSC-521777
Standard InCHIKey:	NISPVUDLMHQFRQ-MKIKIEMVSA-N
Standard InCHI:	InChI=1S/C30H42O7/c1-25(2,36)12-11-21(33)30(8,37)23-19(32)14-27(5)20-10-9-16-17(13-18(31)24(35)26(16,3)4)29(20,7)22(34)15-28(23,27)6/h9,11-13,17,19-20,23,31-32,36-37H,10,14-15H2,1-8H3/b12-11+/t17-,19-,20+,23+,27+,28-,29+,30+/m1/s1
SMILES:	CC(C)(/C=C/C(=O)[C@@](C)([C@H]1[C@@H](C[C@@]2(C)[C@@H]3CC=C4[C@@H](C=C(C(=O)C4(C)C)O)[C@]3(C)C(=O)C[C@]12C)O)O)O
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL387737
PubChem CID:	5281321
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000258] Steroids and steroid derivatives [CHEMONTID:0001686] Cucurbitacins

*Note: the InCHIKey will be temporarily assigned as the "Common Name" if no IUPAC name or alternative short name is available.
**Note: the Chemical Classification was calculated by NPClassifier Version 1.5. Reference: PMID:34662515.

Species Source

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Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO32650	conobea scoparioides	Species	Plantaginaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[7852999]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	PMID[33269591]
NPO32449	eleaocarpus chinensis	Species	n.a.	n.a.	n.a.	n.a.	n.a.	PMID[22239601]
NPO40156	Hemsleya endecaphylla	Species	Cucurbitaceae	Eukaryota	Tubers	n.a.	n.a.	PMID[18088099]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16511	Iberis amara	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[UNPD]
NPO16511	Iberis amara	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]
NPO21876	Trichosanthes cucumeroides	Species	Cucurbitaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]
NPO16511	Iberis amara	Species	Brassicaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCM_Taiwan]

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☑ 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

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Organism ID	NP ID	Organism Material Preparation	Organism Part	NP Quantity (Standard)	NP Quantity (Minimum)	NP Quantity (Maximum)	Quantity Unit	Reference
No data available in table

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☑ 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
EC50	3
GI50	130
IC50	13
Others	12

Activity Type	# Activity
Cell Line	145
Individual Protein	1
NON-MOLECULAR	5
Organism	1
Others	6

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Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT81	Cell Line	A549	Homo sapiens	IC50	=	140.0	nM	PMID[570180]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	60.7	nM	PMID[570179]
NPT139	Cell Line	HT-29	Homo sapiens	IC50	=	190.0	nM	PMID[570178]
NPT368	Cell Line	SN12C	Homo sapiens	GI50	n.a.	430.53	nM	PMID[570177]
NPT369	Cell Line	ACHN	Homo sapiens	GI50	n.a.	267.92	nM	PMID[570177]
NPT370	Cell Line	NCI-H23	Homo sapiens	GI50	n.a.	1327.39	nM	PMID[570177]
NPT371	Cell Line	UO-31	Homo sapiens	GI50	n.a.	195.43	nM	PMID[570177]
NPT372	Cell Line	HOP-92	Homo sapiens	GI50	n.a.	254.68	nM	PMID[570177]
NPT116	Cell Line	HL-60	Homo sapiens	GI50	n.a.	265.46	nM	PMID[570177]
NPT374	Cell Line	SF-539	Homo sapiens	GI50	n.a.	253.51	nM	PMID[570177]

Showing 1 to 10 of 155 entries

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☑ Note for Activity Records:
☉ The quantitative biological activities were primarily integrated from ChEMBL (Version-30) database and were also directly collected from PubMed literature. PubMed PMID was provided as the reference link for each activity record.

Chemically structural similarity: I. Similar Active Natural Products in NPASS

Top-200 similar NPs were calculated against the active-NP-set (includes 4,3285 NPs with experimentally-derived bioactivity available in NPASS)

Similarity level is defined by Tanimoto coefficient (Tc) between two molecules. Tc lies between [0, 1] where '1' indicates the highest similarity. What is Tanimoto coefficient

● The left chart: Distribution of similarity level between NPC111323 and all remaining natural products in the NPASS database.
● The right table: Most similar natural products (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	186
0.1-0.2	1129
0.2-0.3	4442
0.3-0.4	10319
0.4-0.5	11955
0.5-0.6	7743
0.6-0.7	5214
0.7-0.8	1470
0.8-0.85	196
0.85-0.9	36
0.9-0.95	6
0.95-1	1

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Similarity Score	Similarity Level	Natural Product ID
0.9688	High Similarity	NPC87351
0.9588	High Similarity	NPC311612
0.93	High Similarity	NPC185
0.9278	High Similarity	NPC474720
0.9263	High Similarity	NPC472932

Showing 1 to 5 of 200 entries

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Chemically structural similarity: II. Similar Clinical/Approved Drugs

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

● The left chart: Distribution of similarity level between NPC111323 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	161
0.1-0.2	1425
0.2-0.3	3865
0.3-0.4	2532
0.4-0.5	684
0.5-0.6	187
0.6-0.7	138
0.7-0.8	119
0.8-0.85	33
0.85-0.9	6
0.9-0.95	0
0.95-1	0

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Similarity Score	Similarity Level	Drug ID	Developmental Stage
0.89	High Similarity	NPD5211	Phase 2
0.8725	High Similarity	NPD5141	Approved
0.87	High Similarity	NPD5286	Approved
0.87	High Similarity	NPD4696	Approved
0.87	High Similarity	NPD5285	Approved

Showing 1 to 5 of 200 entries

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Bioactivity similarity: Similar Natural Products in NPASS

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