NPASS Compound

Structure

NPC114378 OpenBabel07101718292D 39 43 0 0 1 0 0 0 0 0999 V2000 7.8035 -1.5664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.3149 -0.7201 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -2.4106 0.1761 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5398 -0.2676 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2872 -2.0551 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.4128 0.4903 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 4.2872 1.8540 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.9213 -0.6270 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5945 -1.0778 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.4409 -1.5664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.2658 1.4462 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9799 -0.1005 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.9799 -3.0323 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -0.0828 1.5791 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1336 -2.5437 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 3.2377 1.3440 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1336 0.3881 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 0.8612 1.3262 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8262 -4.4982 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 2.5945 -0.1005 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 1.8683 0.5534 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 5.9799 -1.0778 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2872 -1.0778 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 6.8262 -2.5437 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 -0.6150 0.7595 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 6.8262 -5.4755 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 7.6726 -4.0096 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 6.8262 -1.5664 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 -1.5910 0.7083 0.0000 C 0 0 0 0 0 0 0 0 0 0 0 0 5.1336 -1.5664 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 3.4409 0.3881 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 4.2872 -0.1005 0.0000 C 0 0 1 0 0 0 0 0 0 0 0 0 0.9124 0.3502 0.0000 C 0 0 2 0 0 0 0 0 0 0 0 0 5.9799 -5.9641 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6726 -5.9641 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 8.5189 -4.4982 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 -2.1232 1.5279 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 7.6726 -3.0323 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 0.0000 -0.0000 0.0000 O 0 0 0 0 0 0 0 0 0 0 0 0 1 28 1 0 0 0 0 2 28 1 0 0 0 0 3 29 1 0 0 0 0 4 29 1 0 0 0 0 6 31 1 0 0 0 0 9 10 1 0 0 0 0 9 20 1 0 0 0 0 10 23 1 0 0 0 0 11 16 1 0 0 0 0 12 17 1 0 0 0 0 12 22 1 0 0 0 0 13 15 1 0 0 0 0 13 24 1 0 0 0 0 14 18 1 0 0 0 0 14 25 1 0 0 0 0 15 30 1 0 0 0 0 16 31 1 0 0 0 0 17 32 1 0 0 0 0 18 33 1 0 0 0 0 19 26 1 0 0 0 0 19 27 1 0 0 0 0 20 21 1 0 0 0 0 20 31 1 6 0 0 0 21 11 1 1 0 0 0 21 33 1 0 0 0 0 22 28 1 0 0 0 0 22 30 1 1 0 0 0 23 30 1 1 0 0 0 23 32 1 0 0 0 0 24 28 1 0 0 0 0 24 38 1 6 0 0 0 25 29 1 1 0 0 0 25 39 1 0 0 0 0 26 34 2 0 0 0 0 26 35 1 0 0 0 0 27 36 2 0 0 0 0 27 38 1 0 0 0 0 29 37 1 0 0 0 0 30 5 1 1 0 0 0 31 32 1 1 0 0 0 32 7 1 1 0 0 0 33 8 1 6 0 0 0 33 39 1 0 0 0 0 M END $$$$

Physi-Chem Properties

Molecular Weight:	546.39
Volume:	584.01
LogP:	5.495
LogD:	4.741
LogS:	-4.932
# Rotatable Bonds:	6
TPSA:	93.06
# H-Bond Aceptor:	6
# H-Bond Donor:	2
# Rings:	5
# Heavy Atoms:	6

MedChem Properties

QED Drug-Likeness Score:	0.292
Synthetic Accessibility Score:	4.919
Fsp3:	0.939
Lipinski Rule-of-5:	Rejected
Pfizer Rule:	Accepted
GSK Rule:	Rejected
BMS Rule:	0
Golden Triangle Rule:	Rejected
Chelating Alert:	0
PAINS Alert:	0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:	-5.268
MDCK Permeability:	5.068436803412624e-05
Pgp-inhibitor:	0.596
Pgp-substrate:	0.0
Human Intestinal Absorption (HIA):	0.003
20% Bioavailability (F20%):	0.003
30% Bioavailability (F30%):	0.652

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):	0.014
Plasma Protein Binding (PPB):	93.1357192993164%
Volume Distribution (VD):	0.758
Pgp-substrate:	2.9713141918182373%

ADMET: Metabolism

CYP1A2-inhibitor:	0.006
CYP1A2-substrate:	0.212
CYP2C19-inhibitor:	0.027
CYP2C19-substrate:	0.901
CYP2C9-inhibitor:	0.149
CYP2C9-substrate:	0.873
CYP2D6-inhibitor:	0.001
CYP2D6-substrate:	0.257
CYP3A4-inhibitor:	0.106
CYP3A4-substrate:	0.183

ADMET: Excretion

Clearance (CL):	2.556
Half-life (T1/2):	0.425

ADMET: Toxicity

hERG Blockers:	0.093
Human Hepatotoxicity (H-HT):	0.216
Drug-inuced Liver Injury (DILI):	0.037
AMES Toxicity:	0.003
Rat Oral Acute Toxicity:	0.023
Maximum Recommended Daily Dose:	0.304
Skin Sensitization:	0.944
Carcinogencity:	0.013
Eye Corrosion:	0.95
Eye Irritation:	0.761
Respiratory Toxicity:	0.973

Download Data

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

Natural Product: NPC114378

Natural Product ID:	NPC114378
*Common Name:**	3-O-Malonylepiocotillol Ii
IUPAC Name:	3-[[(3R,5R,8R,9R,10R,13R,14R,17S)-17-[(2S,5R)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-yl]oxy]-3-oxopropanoic acid
Synonyms:	3-O-malonylepiocotillol II
Standard InCHIKey:	PYEPYIQOBUHNRP-ZLPWZIBNSA-N
Standard InCHI:	InChI=1S/C33H54O6/c1-28(2)22-12-17-32(7)23(30(22,5)15-13-24(28)38-27(36)19-26(34)35)10-9-20-21(11-16-31(20,32)6)33(8)18-14-25(39-33)29(3,4)37/h20-25,37H,9-19H2,1-8H3,(H,34,35)/t20-,21+,22+,23-,24-,25-,30+,31-,32-,33+/m1/s1
SMILES:	OC(=O)CC(=O)O[C@@H]1CC[C@]2([C@H](C1(C)C)CC[C@@]1([C@@H]2CC[C@H]2[C@@]1(C)CC[C@@H]2[C@]1(C)CC[C@@H](O1)C(O)(C)C)C)C
Synthetic Gene Cluster:	n.a.
ChEMBL Identifier:	CHEMBL224431
PubChem CID:	44421634
Chemical Classification:**	CHEMONTID:0000000 [Organic compounds] [CHEMONTID:0000012] Lipids and lipid-like molecules [CHEMONTID:0000259] Prenol lipids [CHEMONTID:0002049] Terpene glycosides [CHEMONTID:0001580] Triterpene glycosides [CHEMONTID:0002358] Triterpene saponins

*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

Organism ID	Organism Name	Taxonomy Level	Family	SuperKingdom	Isolation Part	Collection Location	Collection Time	Reference
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	floral spikes	n.a.	n.a.	PMID[17346076]
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	bark	n.a.	n.a.	PMID[9873651]
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[HerDing]
NPO4138.1	Betula platyphylla var. japonica	Varieties	Betulaceae	Eukaryota	n.a.	n.a.	n.a.	Database[TCMID]

☑ 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	NP ID	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	8

Activity Type	# Activity
Cell Line	4
Others	4

Target ID	Target Type	Target Name	Target Organism	Activity Type	Activity Relation	Value	Unit	Reference
NPT91	Cell Line	KB	Homo sapiens	IC50	=	60800.0	nM	PMID[550335]
NPT111	Cell Line	K562	Homo sapiens	IC50	=	57500.0	nM	PMID[550335]
NPT83	Cell Line	MCF7	Homo sapiens	IC50	=	64100.0	nM	PMID[550335]
NPT407	Cell Line	COLO 205	Homo sapiens	IC50	=	55600.0	nM	PMID[550335]
NPT27	Others	Unspecified		IC50	=	69600.0	nM	PMID[550335]
NPT27	Others	Unspecified		IC50	=	65500.0	nM	PMID[550335]
NPT27	Others	Unspecified		IC50	=	47200.0	nM	PMID[550335]
NPT27	Others	Unspecified		IC50	=	42500.0	nM	PMID[550335]

☑ 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 NPC114378 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	387
0.1-0.2	3357
0.2-0.3	10380
0.3-0.4	13494
0.4-0.5	5688
0.5-0.6	5209
0.6-0.7	3323
0.7-0.8	777
0.8-0.85	57
0.85-0.9	13
0.9-0.95	8
0.95-1	4

Similarity Score	Similarity Level	Natural Product ID
1.0	High Similarity	NPC103782
0.9756	High Similarity	NPC201607
0.9756	High Similarity	NPC56777
0.9375	High Similarity	NPC190940
0.9259	High Similarity	NPC286719
0.9259	High Similarity	NPC477286
0.9146	High Similarity	NPC477285
0.9146	High Similarity	NPC111582
0.9048	High Similarity	NPC477283
0.9048	High Similarity	NPC155531
0.9048	High Similarity	NPC215968
0.8659	High Similarity	NPC477287
0.8642	High Similarity	NPC133596
0.8642	High Similarity	NPC212453
0.8642	High Similarity	NPC11907
0.8571	High Similarity	NPC202688
0.8571	High Similarity	NPC116683
0.8571	High Similarity	NPC477284
0.8571	High Similarity	NPC60018
0.8571	High Similarity	NPC154043
0.8539	High Similarity	NPC473066
0.8434	Intermediate Similarity	NPC81074
0.8434	Intermediate Similarity	NPC477282
0.8434	Intermediate Similarity	NPC220379
0.8415	Intermediate Similarity	NPC64081
0.8415	Intermediate Similarity	NPC474574
0.8395	Intermediate Similarity	NPC91387
0.8395	Intermediate Similarity	NPC270306
0.8395	Intermediate Similarity	NPC231680
0.8353	Intermediate Similarity	NPC311642
0.8353	Intermediate Similarity	NPC13494
0.8353	Intermediate Similarity	NPC100366
0.8353	Intermediate Similarity	NPC242771
0.8353	Intermediate Similarity	NPC164289
0.8276	Intermediate Similarity	NPC266651
0.8256	Intermediate Similarity	NPC268578
0.8256	Intermediate Similarity	NPC217559
0.8256	Intermediate Similarity	NPC292458
0.8242	Intermediate Similarity	NPC182740
0.8242	Intermediate Similarity	NPC256104
0.8242	Intermediate Similarity	NPC122083
0.8242	Intermediate Similarity	NPC211845
0.8235	Intermediate Similarity	NPC73515
0.8214	Intermediate Similarity	NPC476176
0.8193	Intermediate Similarity	NPC171658
0.8182	Intermediate Similarity	NPC80700
0.8172	Intermediate Similarity	NPC237071
0.8172	Intermediate Similarity	NPC156377
0.8172	Intermediate Similarity	NPC203434
0.8172	Intermediate Similarity	NPC238796
0.8161	Intermediate Similarity	NPC473336
0.8161	Intermediate Similarity	NPC319909
0.8161	Intermediate Similarity	NPC471044
0.814	Intermediate Similarity	NPC477936
0.814	Intermediate Similarity	NPC102156
0.814	Intermediate Similarity	NPC475388
0.814	Intermediate Similarity	NPC148740
0.8118	Intermediate Similarity	NPC472943
0.8118	Intermediate Similarity	NPC472951
0.8111	Intermediate Similarity	NPC56962
0.8111	Intermediate Similarity	NPC24705
0.8095	Intermediate Similarity	NPC471045
0.8049	Intermediate Similarity	NPC472944
0.8049	Intermediate Similarity	NPC472945
0.8046	Intermediate Similarity	NPC470070
0.8023	Intermediate Similarity	NPC470154
0.8023	Intermediate Similarity	NPC58631
0.8	Intermediate Similarity	NPC80891
0.8	Intermediate Similarity	NPC31302
0.8	Intermediate Similarity	NPC471221
0.8	Intermediate Similarity	NPC201276
0.8	Intermediate Similarity	NPC245029
0.7978	Intermediate Similarity	NPC92139
0.7978	Intermediate Similarity	NPC131365
0.7957	Intermediate Similarity	NPC191915
0.7957	Intermediate Similarity	NPC151214
0.7955	Intermediate Similarity	NPC18953
0.7952	Intermediate Similarity	NPC186851
0.7931	Intermediate Similarity	NPC121121
0.7931	Intermediate Similarity	NPC477446
0.7931	Intermediate Similarity	NPC477447
0.7931	Intermediate Similarity	NPC477935
0.7931	Intermediate Similarity	NPC470155
0.7917	Intermediate Similarity	NPC470030
0.7912	Intermediate Similarity	NPC61688
0.7912	Intermediate Similarity	NPC82955
0.7907	Intermediate Similarity	NPC261616
0.7907	Intermediate Similarity	NPC474714
0.7895	Intermediate Similarity	NPC253586
0.7889	Intermediate Similarity	NPC5943
0.7889	Intermediate Similarity	NPC210658
0.7889	Intermediate Similarity	NPC161928
0.7882	Intermediate Similarity	NPC34046
0.7882	Intermediate Similarity	NPC224802
0.7882	Intermediate Similarity	NPC80089
0.7882	Intermediate Similarity	NPC324700
0.7882	Intermediate Similarity	NPC171426
0.7872	Intermediate Similarity	NPC94582
0.7872	Intermediate Similarity	NPC21897
0.7872	Intermediate Similarity	NPC57964
0.7835	Intermediate Similarity	NPC476512
0.7835	Intermediate Similarity	NPC108227
0.7835	Intermediate Similarity	NPC472081
0.7835	Intermediate Similarity	NPC475574
0.7826	Intermediate Similarity	NPC473269
0.7826	Intermediate Similarity	NPC470114
0.7816	Intermediate Similarity	NPC12933
0.7816	Intermediate Similarity	NPC470156
0.7812	Intermediate Similarity	NPC292775
0.7805	Intermediate Similarity	NPC157777
0.7805	Intermediate Similarity	NPC131506
0.7802	Intermediate Similarity	NPC476435
0.7802	Intermediate Similarity	NPC128475
0.7789	Intermediate Similarity	NPC252056
0.7778	Intermediate Similarity	NPC471411
0.7778	Intermediate Similarity	NPC472272
0.7778	Intermediate Similarity	NPC474448
0.7778	Intermediate Similarity	NPC302111
0.7778	Intermediate Similarity	NPC471410
0.7778	Intermediate Similarity	NPC107919
0.7766	Intermediate Similarity	NPC206878
0.7765	Intermediate Similarity	NPC477918
0.7765	Intermediate Similarity	NPC471151
0.7755	Intermediate Similarity	NPC114700
0.7755	Intermediate Similarity	NPC470029
0.7755	Intermediate Similarity	NPC134967
0.7755	Intermediate Similarity	NPC310138
0.7753	Intermediate Similarity	NPC65133
0.7753	Intermediate Similarity	NPC477434
0.7753	Intermediate Similarity	NPC320824
0.7742	Intermediate Similarity	NPC219516
0.7742	Intermediate Similarity	NPC210759
0.7742	Intermediate Similarity	NPC229801
0.7742	Intermediate Similarity	NPC307167
0.7738	Intermediate Similarity	NPC158208
0.7738	Intermediate Similarity	NPC196136
0.7738	Intermediate Similarity	NPC477934
0.7738	Intermediate Similarity	NPC317242
0.7738	Intermediate Similarity	NPC243027
0.7732	Intermediate Similarity	NPC108371
0.7727	Intermediate Similarity	NPC470611
0.7717	Intermediate Similarity	NPC200580
0.7717	Intermediate Similarity	NPC269267
0.7717	Intermediate Similarity	NPC228059
0.7717	Intermediate Similarity	NPC20822
0.7711	Intermediate Similarity	NPC473238
0.7711	Intermediate Similarity	NPC153719
0.7711	Intermediate Similarity	NPC472341
0.7701	Intermediate Similarity	NPC16449
0.7701	Intermediate Similarity	NPC472853
0.77	Intermediate Similarity	NPC472655
0.7692	Intermediate Similarity	NPC45833
0.7692	Intermediate Similarity	NPC43912
0.7692	Intermediate Similarity	NPC252714
0.7692	Intermediate Similarity	NPC263802
0.7692	Intermediate Similarity	NPC213658
0.7692	Intermediate Similarity	NPC140446
0.7692	Intermediate Similarity	NPC202937
0.7692	Intermediate Similarity	NPC62202
0.7692	Intermediate Similarity	NPC110365
0.7677	Intermediate Similarity	NPC139181
0.7677	Intermediate Similarity	NPC476837
0.7677	Intermediate Similarity	NPC97260
0.7674	Intermediate Similarity	NPC252483
0.7674	Intermediate Similarity	NPC191345
0.767	Intermediate Similarity	NPC272242
0.7667	Intermediate Similarity	NPC290612
0.7667	Intermediate Similarity	NPC131350
0.766	Intermediate Similarity	NPC476189
0.766	Intermediate Similarity	NPC311246
0.766	Intermediate Similarity	NPC167644
0.7653	Intermediate Similarity	NPC178853
0.7647	Intermediate Similarity	NPC136424
0.7647	Intermediate Similarity	NPC163597
0.7647	Intermediate Similarity	NPC477932
0.7647	Intermediate Similarity	NPC4209
0.7647	Intermediate Similarity	NPC470145
0.7647	Intermediate Similarity	NPC477933
0.764	Intermediate Similarity	NPC29342
0.764	Intermediate Similarity	NPC69953
0.764	Intermediate Similarity	NPC259173
0.764	Intermediate Similarity	NPC2572
0.7634	Intermediate Similarity	NPC185529
0.7634	Intermediate Similarity	NPC473542
0.7634	Intermediate Similarity	NPC472146
0.7629	Intermediate Similarity	NPC474092
0.7619	Intermediate Similarity	NPC10476
0.7619	Intermediate Similarity	NPC228994
0.7619	Intermediate Similarity	NPC74639
0.7619	Intermediate Similarity	NPC272359
0.7619	Intermediate Similarity	NPC192501
0.7614	Intermediate Similarity	NPC119922
0.7614	Intermediate Similarity	NPC116320
0.7609	Intermediate Similarity	NPC250687
0.7609	Intermediate Similarity	NPC254572
0.7609	Intermediate Similarity	NPC229407
0.7609	Intermediate Similarity	NPC48824
0.7609	Intermediate Similarity	NPC476379
0.7604	Intermediate Similarity	NPC296936
0.7604	Intermediate Similarity	NPC193785

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 NPC114378 and all drugs/candidates.
● The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

range	Tanimoto Coefficient
0-0.1	404
0.1-0.2	3619
0.2-0.3	3499
0.3-0.4	1001
0.4-0.5	278
0.5-0.6	261
0.6-0.7	75
0.7-0.8	13
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
0.7882	Intermediate Similarity	NPD6118	Approved
0.7882	Intermediate Similarity	NPD6114	Approved
0.7882	Intermediate Similarity	NPD6115	Approved
0.7882	Intermediate Similarity	NPD6697	Approved
0.7778	Intermediate Similarity	NPD4267	Clinical (unspecified phase)
0.7647	Intermediate Similarity	NPD6117	Approved
0.7558	Intermediate Similarity	NPD6116	Phase 1
0.7412	Intermediate Similarity	NPD6113	Clinical (unspecified phase)
0.7292	Intermediate Similarity	NPD8171	Discontinued
0.7111	Intermediate Similarity	NPD6928	Phase 2
0.7087	Intermediate Similarity	NPD8170	Clinical (unspecified phase)
0.701	Intermediate Similarity	NPD8035	Phase 2
0.701	Intermediate Similarity	NPD8034	Phase 2
0.6977	Remote Similarity	NPD4808	Clinical (unspecified phase)
0.6977	Remote Similarity	NPD4809	Clinical (unspecified phase)
0.6961	Remote Similarity	NPD1700	Approved
0.6932	Remote Similarity	NPD3702	Approved
0.6932	Remote Similarity	NPD3703	Phase 2
0.6824	Remote Similarity	NPD5361	Clinical (unspecified phase)
0.6824	Remote Similarity	NPD5360	Phase 3
0.6782	Remote Similarity	NPD5777	Approved
0.6782	Remote Similarity	NPD6081	Approved
0.6744	Remote Similarity	NPD3700	Clinical (unspecified phase)
0.6744	Remote Similarity	NPD3699	Clinical (unspecified phase)
0.6737	Remote Similarity	NPD7520	Clinical (unspecified phase)
0.6667	Remote Similarity	NPD4787	Phase 1
0.6602	Remote Similarity	NPD7638	Approved
0.6588	Remote Similarity	NPD4224	Phase 2
0.6577	Remote Similarity	NPD8133	Approved
0.6574	Remote Similarity	NPD5345	Clinical (unspecified phase)
0.6555	Remote Similarity	NPD7736	Approved
0.6538	Remote Similarity	NPD7640	Approved
0.6538	Remote Similarity	NPD7639	Approved
0.6538	Remote Similarity	NPD8418	Phase 2
0.6522	Remote Similarity	NPD8377	Approved
0.6522	Remote Similarity	NPD8294	Approved
0.6491	Remote Similarity	NPD7327	Approved
0.6491	Remote Similarity	NPD7328	Approved
0.6477	Remote Similarity	NPD4789	Approved
0.6477	Remote Similarity	NPD4245	Approved
0.6477	Remote Similarity	NPD4244	Approved
0.6471	Remote Similarity	NPD8293	Discontinued
0.6466	Remote Similarity	NPD8380	Approved
0.6466	Remote Similarity	NPD8379	Approved
0.6466	Remote Similarity	NPD8296	Approved
0.6466	Remote Similarity	NPD8335	Approved
0.6466	Remote Similarity	NPD8033	Approved
0.6466	Remote Similarity	NPD8378	Approved
0.6442	Remote Similarity	NPD4225	Approved
0.6441	Remote Similarity	NPD7492	Approved
0.6435	Remote Similarity	NPD7516	Approved
0.6415	Remote Similarity	NPD7632	Discontinued
0.6404	Remote Similarity	NPD4758	Discontinued
0.6404	Remote Similarity	NPD7115	Discovery
0.6387	Remote Similarity	NPD6616	Approved
0.6383	Remote Similarity	NPD7525	Registered
0.6379	Remote Similarity	NPD6059	Approved
0.6379	Remote Similarity	NPD6319	Approved
0.6379	Remote Similarity	NPD6054	Approved
0.6364	Remote Similarity	NPD3698	Phase 2
0.6364	Remote Similarity	NPD7319	Approved
0.6354	Remote Similarity	NPD3670	Clinical (unspecified phase)
0.6354	Remote Similarity	NPD3669	Approved
0.6353	Remote Similarity	NPD371	Approved
0.6344	Remote Similarity	NPD5364	Discontinued
0.6339	Remote Similarity	NPD8297	Approved
0.6333	Remote Similarity	NPD7078	Approved
0.6316	Remote Similarity	NPD6940	Discontinued
0.6311	Remote Similarity	NPD7991	Discontinued
0.6279	Remote Similarity	NPD3171	Clinical (unspecified phase)
0.6275	Remote Similarity	NPD6399	Phase 3
0.6273	Remote Similarity	NPD7320	Approved
0.6271	Remote Similarity	NPD6370	Approved
0.6261	Remote Similarity	NPD8295	Clinical (unspecified phase)
0.625	Remote Similarity	NPD7507	Approved
0.6239	Remote Similarity	NPD6675	Approved
0.6239	Remote Similarity	NPD5739	Approved
0.6239	Remote Similarity	NPD6402	Approved
0.6239	Remote Similarity	NPD7128	Approved
0.6216	Remote Similarity	NPD8132	Clinical (unspecified phase)
0.6216	Remote Similarity	NPD4061	Clinical (unspecified phase)
0.6214	Remote Similarity	NPD7748	Approved
0.6186	Remote Similarity	NPD6015	Approved
0.6186	Remote Similarity	NPD6016	Approved
0.6176	Remote Similarity	NPD7637	Suspended
0.617	Remote Similarity	NPD3671	Phase 1
0.614	Remote Similarity	NPD4632	Approved
0.6134	Remote Similarity	NPD5988	Approved
0.6126	Remote Similarity	NPD6881	Approved
0.6126	Remote Similarity	NPD6899	Approved
0.6111	Remote Similarity	NPD7532	Clinical (unspecified phase)
0.6106	Remote Similarity	NPD8130	Phase 1
0.61	Remote Similarity	NPD7524	Approved
0.6091	Remote Similarity	NPD6008	Approved
0.6071	Remote Similarity	NPD6373	Approved
0.6071	Remote Similarity	NPD6372	Approved
0.6038	Remote Similarity	NPD7902	Approved
0.6038	Remote Similarity	NPD6084	Phase 2
0.6038	Remote Similarity	NPD6083	Phase 2
0.6036	Remote Similarity	NPD5701	Approved
0.6036	Remote Similarity	NPD5697	Approved
0.6018	Remote Similarity	NPD4634	Approved
0.6018	Remote Similarity	NPD7102	Approved
0.6018	Remote Similarity	NPD5955	Clinical (unspecified phase)
0.6018	Remote Similarity	NPD7290	Approved
0.6018	Remote Similarity	NPD6883	Approved
0.6	Remote Similarity	NPD4802	Phase 2
0.6	Remote Similarity	NPD4238	Approved
0.6	Remote Similarity	NPD6356	Clinical (unspecified phase)
0.6	Remote Similarity	NPD8308	Discontinued
0.5965	Remote Similarity	NPD6617	Approved
0.5965	Remote Similarity	NPD6650	Approved
0.5965	Remote Similarity	NPD6847	Approved
0.5965	Remote Similarity	NPD6649	Approved
0.5965	Remote Similarity	NPD6869	Approved
0.595	Remote Similarity	NPD8328	Phase 3
0.5929	Remote Similarity	NPD6012	Approved
0.5929	Remote Similarity	NPD6014	Approved
0.5929	Remote Similarity	NPD6013	Approved
0.5922	Remote Similarity	NPD6700	Approved
0.5922	Remote Similarity	NPD6701	Clinical (unspecified phase)
0.5917	Remote Similarity	NPD7503	Approved
0.5917	Remote Similarity	NPD6921	Approved
0.5914	Remote Similarity	NPD1811	Approved
0.5914	Remote Similarity	NPD1810	Approved
0.5913	Remote Similarity	NPD6882	Approved
0.5893	Remote Similarity	NPD6412	Phase 2
0.5889	Remote Similarity	NPD229	Approved
0.5887	Remote Similarity	NPD6033	Approved
0.5865	Remote Similarity	NPD6703	Approved
0.5865	Remote Similarity	NPD7515	Phase 2
0.5865	Remote Similarity	NPD6702	Approved
0.5859	Remote Similarity	NPD4788	Approved
0.5859	Remote Similarity	NPD6695	Phase 3
0.5856	Remote Similarity	NPD4056	Clinical (unspecified phase)
0.5856	Remote Similarity	NPD4057	Clinical (unspecified phase)
0.5849	Remote Similarity	NPD5695	Phase 3
0.5847	Remote Similarity	NPD6009	Approved
0.5841	Remote Similarity	NPD6011	Approved
0.5833	Remote Similarity	NPD5696	Approved
0.5826	Remote Similarity	NPD6401	Clinical (unspecified phase)
0.5825	Remote Similarity	NPD5328	Approved
0.5825	Remote Similarity	NPD6051	Approved
0.582	Remote Similarity	NPD7604	Phase 2
0.5816	Remote Similarity	NPD1780	Approved
0.5816	Remote Similarity	NPD1779	Approved
0.58	Remote Similarity	NPD7338	Clinical (unspecified phase)
0.58	Remote Similarity	NPD4786	Approved
0.5785	Remote Similarity	NPD5983	Phase 2
0.5784	Remote Similarity	NPD7750	Discontinued
0.5773	Remote Similarity	NPD7645	Phase 2
0.5761	Remote Similarity	NPD2687	Approved
0.5761	Remote Similarity	NPD2254	Approved
0.5761	Remote Similarity	NPD2686	Approved
0.5755	Remote Similarity	NPD7901	Clinical (unspecified phase)
0.5755	Remote Similarity	NPD7900	Approved
0.5752	Remote Similarity	NPD5954	Clinical (unspecified phase)
0.5741	Remote Similarity	NPD4755	Approved
0.5728	Remote Similarity	NPD5737	Approved
0.5728	Remote Similarity	NPD7513	Clinical (unspecified phase)
0.5728	Remote Similarity	NPD6903	Approved
0.5728	Remote Similarity	NPD6672	Approved
0.5726	Remote Similarity	NPD8298	Phase 2
0.5726	Remote Similarity	NPD6336	Discontinued
0.5714	Remote Similarity	NPD6079	Approved
0.5702	Remote Similarity	NPD8174	Phase 2
0.5702	Remote Similarity	NPD6686	Approved
0.5686	Remote Similarity	NPD5330	Approved
0.5686	Remote Similarity	NPD6684	Approved
0.5686	Remote Similarity	NPD7146	Approved
0.5686	Remote Similarity	NPD7521	Approved
0.5686	Remote Similarity	NPD6409	Approved
0.5686	Remote Similarity	NPD3618	Phase 1
0.5686	Remote Similarity	NPD7334	Approved
0.5686	Remote Similarity	NPD3574	Clinical (unspecified phase)
0.5684	Remote Similarity	NPD6942	Approved
0.5684	Remote Similarity	NPD7339	Approved
0.5664	Remote Similarity	NPD6920	Discontinued
0.566	Remote Similarity	NPD4202	Approved
0.5636	Remote Similarity	NPD4696	Approved
0.5636	Remote Similarity	NPD5285	Approved
0.5636	Remote Similarity	NPD4700	Approved
0.5636	Remote Similarity	NPD5286	Approved
0.563	Remote Similarity	NPD7754	Approved
0.563	Remote Similarity	NPD7755	Approved
0.563	Remote Similarity	NPD6274	Approved
0.5625	Remote Similarity	NPD6933	Approved
0.562	Remote Similarity	NPD7101	Approved
0.562	Remote Similarity	NPD7100	Approved
0.5618	Remote Similarity	NPD7909	Approved
0.5614	Remote Similarity	NPD7646	Clinical (unspecified phase)
0.5607	Remote Similarity	NPD6001	Approved
0.56	Remote Similarity	NPD3667	Approved

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