Structure

Physi-Chem Properties

Molecular Weight:  222.2
Volume:  257.037
LogP:  3.567
LogD:  3.33
LogS:  -4.106
# Rotatable Bonds:  1
TPSA:  20.23
# H-Bond Aceptor:  1
# H-Bond Donor:  1
# Rings:  2
# Heavy Atoms:  1

MedChem Properties

QED Drug-Likeness Score:  0.669
Synthetic Accessibility Score:  4.437
Fsp3:  0.867
Lipinski Rule-of-5:  Accepted
Pfizer Rule:  Rejected
GSK Rule:  Accepted
BMS Rule:  0
Golden Triangle Rule:  Accepted
Chelating Alert:  0
PAINS Alert:  0

ADMET Properties (ADMETlab2.0)

ADMET: Absorption

Caco-2 Permeability:  -4.299
MDCK Permeability:  2.3958013116498478e-05
Pgp-inhibitor:  0.014
Pgp-substrate:  0.001
Human Intestinal Absorption (HIA):  0.003
20% Bioavailability (F20%):  0.073
30% Bioavailability (F30%):  0.709

ADMET: Distribution

Blood-Brain-Barrier Penetration (BBB):  0.13
Plasma Protein Binding (PPB):  92.4853744506836%
Volume Distribution (VD):  0.904
Pgp-substrate:  6.395586013793945%

ADMET: Metabolism

CYP1A2-inhibitor:  0.155
CYP1A2-substrate:  0.558
CYP2C19-inhibitor:  0.06
CYP2C19-substrate:  0.908
CYP2C9-inhibitor:  0.051
CYP2C9-substrate:  0.108
CYP2D6-inhibitor:  0.022
CYP2D6-substrate:  0.172
CYP3A4-inhibitor:  0.575
CYP3A4-substrate:  0.632

ADMET: Excretion

Clearance (CL):  8.424
Half-life (T1/2):  0.417

ADMET: Toxicity

hERG Blockers:  0.018
Human Hepatotoxicity (H-HT):  0.176
Drug-inuced Liver Injury (DILI):  0.032
AMES Toxicity:  0.006
Rat Oral Acute Toxicity:  0.089
Maximum Recommended Daily Dose:  0.323
Skin Sensitization:  0.932
Carcinogencity:  0.078
Eye Corrosion:  0.512
Eye Irritation:  0.951
Respiratory Toxicity:  0.313

Download Data

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

  Natural Product: NPC309825

Natural Product ID:  NPC309825
Common Name*:   Naviculol
IUPAC Name:   (2E)-2-[(1R,3aS,4R,7aS)-1,3a,4,7a-tetramethyl-1,2,3,4,6,7-hexahydroinden-5-ylidene]ethanol
Synonyms:   Naviculol
Standard InCHIKey:  RMIRDGFNJKHARM-LAPNCVBBSA-N
Standard InCHI:  InChI=1S/C15H26O/c1-11-5-8-15(4)12(2)13(7-10-16)6-9-14(11,15)3/h7,11-12,16H,5-6,8-10H2,1-4H3/b13-7+/t11-,12-,14+,15+/m1/s1
SMILES:  C[C@@H]1/C(=C/CO)/CC[C@@]2([C@@]1(C)CC[C@H]2C)C
Synthetic Gene Cluster:   n.a.
ChEMBL Identifier:   CHEMBL504928
PubChem CID:   14313693
Chemical Classification**:  
  • CHEMONTID:0000000 [Organic compounds]
    • [CHEMONTID:0000012] Lipids and lipid-like molecules
      • [CHEMONTID:0000259] Prenol lipids
        • [CHEMONTID:0001550] Sesquiterpenoids

*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
NPO32961 bazzanianovae-zelandiae Species n.a. n.a. n.a. n.a. n.a. PMID[10785435]

☑ 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

Target ID Target Type Target Name Target Organism Activity Type Activity Relation Value Unit Reference
NPT168 Cell Line P388 Mus musculus GI50 > 25.0 ug.mL-1 PMID[529612]

☑ 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 NPC309825 and all remaining natural products in the NPASS database.
●  The right table: Most similar natural products (Tc>=0.56 or Top200).

Similarity Score Similarity Level Natural Product ID
0.9138 High Similarity NPC234264
0.9138 High Similarity NPC47840
0.8947 High Similarity NPC11130
0.8833 High Similarity NPC124112
0.8689 High Similarity NPC475704
0.8413 Intermediate Similarity NPC135650
0.7969 Intermediate Similarity NPC187619
0.7966 Intermediate Similarity NPC298299
0.7879 Intermediate Similarity NPC160209
0.7857 Intermediate Similarity NPC244488
0.7857 Intermediate Similarity NPC247325
0.7846 Intermediate Similarity NPC162309
0.7833 Intermediate Similarity NPC249645
0.7833 Intermediate Similarity NPC55412
0.7727 Intermediate Similarity NPC68703
0.7727 Intermediate Similarity NPC136813
0.7727 Intermediate Similarity NPC171225
0.7727 Intermediate Similarity NPC69649
0.7719 Intermediate Similarity NPC182102
0.7719 Intermediate Similarity NPC26960
0.7692 Intermediate Similarity NPC19569
0.7681 Intermediate Similarity NPC474743
0.7619 Intermediate Similarity NPC176621
0.7619 Intermediate Similarity NPC471081
0.7612 Intermediate Similarity NPC167527
0.7586 Intermediate Similarity NPC244038
0.7571 Intermediate Similarity NPC309178
0.7538 Intermediate Similarity NPC107540
0.7538 Intermediate Similarity NPC309300
0.7534 Intermediate Similarity NPC84694
0.7534 Intermediate Similarity NPC28862
0.7534 Intermediate Similarity NPC109546
0.7534 Intermediate Similarity NPC47982
0.7534 Intermediate Similarity NPC81306
0.7534 Intermediate Similarity NPC30986
0.7534 Intermediate Similarity NPC209430
0.7534 Intermediate Similarity NPC143182
0.75 Intermediate Similarity NPC469728
0.75 Intermediate Similarity NPC474248
0.75 Intermediate Similarity NPC167272
0.75 Intermediate Similarity NPC147524
0.75 Intermediate Similarity NPC269877
0.7465 Intermediate Similarity NPC313185
0.7463 Intermediate Similarity NPC308522
0.7463 Intermediate Similarity NPC477791
0.7463 Intermediate Similarity NPC114651
0.7463 Intermediate Similarity NPC74885
0.7432 Intermediate Similarity NPC234193
0.7429 Intermediate Similarity NPC474140
0.7397 Intermediate Similarity NPC474216
0.7391 Intermediate Similarity NPC189745
0.7391 Intermediate Similarity NPC9161
0.7391 Intermediate Similarity NPC49422
0.7391 Intermediate Similarity NPC34834
0.7353 Intermediate Similarity NPC471238
0.7353 Intermediate Similarity NPC96484
0.7344 Intermediate Similarity NPC135648
0.7333 Intermediate Similarity NPC23852
0.7333 Intermediate Similarity NPC264245
0.7333 Intermediate Similarity NPC209620
0.7333 Intermediate Similarity NPC4166
0.7324 Intermediate Similarity NPC469534
0.7324 Intermediate Similarity NPC469533
0.7324 Intermediate Similarity NPC469593
0.7313 Intermediate Similarity NPC202017
0.7286 Intermediate Similarity NPC471662
0.7286 Intermediate Similarity NPC477792
0.7273 Intermediate Similarity NPC96793
0.7273 Intermediate Similarity NPC323424
0.7258 Intermediate Similarity NPC48891
0.7246 Intermediate Similarity NPC473893
0.7237 Intermediate Similarity NPC50964
0.7237 Intermediate Similarity NPC218616
0.7237 Intermediate Similarity NPC202389
0.7237 Intermediate Similarity NPC49964
0.7237 Intermediate Similarity NPC101462
0.7237 Intermediate Similarity NPC311092
0.7237 Intermediate Similarity NPC87489
0.7237 Intermediate Similarity NPC296701
0.7237 Intermediate Similarity NPC189972
0.7231 Intermediate Similarity NPC210346
0.7222 Intermediate Similarity NPC141071
0.7222 Intermediate Similarity NPC230301
0.7222 Intermediate Similarity NPC22105
0.7222 Intermediate Similarity NPC28657
0.7222 Intermediate Similarity NPC288035
0.7222 Intermediate Similarity NPC257347
0.7222 Intermediate Similarity NPC471723
0.7222 Intermediate Similarity NPC285893
0.7222 Intermediate Similarity NPC304309
0.7222 Intermediate Similarity NPC134847
0.7222 Intermediate Similarity NPC471468
0.7222 Intermediate Similarity NPC162742
0.7222 Intermediate Similarity NPC136188
0.72 Intermediate Similarity NPC164840
0.72 Intermediate Similarity NPC209944
0.72 Intermediate Similarity NPC241290
0.7183 Intermediate Similarity NPC234527
0.7183 Intermediate Similarity NPC14352
0.7164 Intermediate Similarity NPC238352
0.7164 Intermediate Similarity NPC477009
0.7164 Intermediate Similarity NPC107258
0.7162 Intermediate Similarity NPC473943
0.7162 Intermediate Similarity NPC477514
0.7143 Intermediate Similarity NPC41539
0.7143 Intermediate Similarity NPC475789
0.7143 Intermediate Similarity NPC474634
0.7143 Intermediate Similarity NPC470384
0.7143 Intermediate Similarity NPC317458
0.7123 Intermediate Similarity NPC321016
0.7123 Intermediate Similarity NPC240604
0.7123 Intermediate Similarity NPC134330
0.7123 Intermediate Similarity NPC300324
0.7123 Intermediate Similarity NPC107059
0.7123 Intermediate Similarity NPC46160
0.7123 Intermediate Similarity NPC113733
0.7123 Intermediate Similarity NPC189883
0.7123 Intermediate Similarity NPC321381
0.7123 Intermediate Similarity NPC470362
0.7123 Intermediate Similarity NPC237460
0.7123 Intermediate Similarity NPC202642
0.7123 Intermediate Similarity NPC129165
0.7121 Intermediate Similarity NPC474480
0.7121 Intermediate Similarity NPC474155
0.7121 Intermediate Similarity NPC473759
0.7121 Intermediate Similarity NPC81615
0.7119 Intermediate Similarity NPC200129
0.7105 Intermediate Similarity NPC474731
0.7105 Intermediate Similarity NPC7505
0.7105 Intermediate Similarity NPC474752
0.7105 Intermediate Similarity NPC474759
0.7105 Intermediate Similarity NPC82986
0.7105 Intermediate Similarity NPC47761
0.7105 Intermediate Similarity NPC474683
0.7101 Intermediate Similarity NPC224532
0.7083 Intermediate Similarity NPC329090
0.7083 Intermediate Similarity NPC476366
0.7083 Intermediate Similarity NPC306727
0.7083 Intermediate Similarity NPC27395
0.7083 Intermediate Similarity NPC201048
0.7083 Intermediate Similarity NPC471659
0.7077 Intermediate Similarity NPC240506
0.7059 Intermediate Similarity NPC259156
0.7059 Intermediate Similarity NPC222366
0.7059 Intermediate Similarity NPC242945
0.7059 Intermediate Similarity NPC149680
0.7059 Intermediate Similarity NPC81907
0.7059 Intermediate Similarity NPC250977
0.7059 Intermediate Similarity NPC476039
0.7059 Intermediate Similarity NPC286669
0.7051 Intermediate Similarity NPC231310
0.7051 Intermediate Similarity NPC185568
0.7051 Intermediate Similarity NPC205845
0.7051 Intermediate Similarity NPC474047
0.7051 Intermediate Similarity NPC238485
0.7042 Intermediate Similarity NPC471271
0.7042 Intermediate Similarity NPC471268
0.7042 Intermediate Similarity NPC471272
0.7027 Intermediate Similarity NPC34019
0.7027 Intermediate Similarity NPC198968
0.7027 Intermediate Similarity NPC155986
0.7027 Intermediate Similarity NPC91665
0.7027 Intermediate Similarity NPC214570
0.7027 Intermediate Similarity NPC318495
0.7018 Intermediate Similarity NPC49088
0.7018 Intermediate Similarity NPC86683
0.7015 Intermediate Similarity NPC219940
0.7015 Intermediate Similarity NPC329698
0.7015 Intermediate Similarity NPC290367
0.7015 Intermediate Similarity NPC110241
0.7015 Intermediate Similarity NPC225415
0.7013 Intermediate Similarity NPC470049
0.7 Intermediate Similarity NPC471560
0.6986 Remote Similarity NPC322353
0.6986 Remote Similarity NPC32832
0.6986 Remote Similarity NPC121744
0.6986 Remote Similarity NPC328104
0.6986 Remote Similarity NPC263698
0.6986 Remote Similarity NPC118508
0.6986 Remote Similarity NPC319090
0.6974 Remote Similarity NPC324772
0.6962 Remote Similarity NPC471224
0.6962 Remote Similarity NPC472931
0.6962 Remote Similarity NPC472940
0.6962 Remote Similarity NPC266511
0.6962 Remote Similarity NPC474083
0.6962 Remote Similarity NPC274448
0.6957 Remote Similarity NPC197805
0.6933 Remote Similarity NPC85346
0.6933 Remote Similarity NPC167037
0.6933 Remote Similarity NPC244385
0.6933 Remote Similarity NPC477522
0.6933 Remote Similarity NPC18603
0.6933 Remote Similarity NPC138621
0.6933 Remote Similarity NPC186191
0.6933 Remote Similarity NPC76931
0.6933 Remote Similarity NPC65897
0.6933 Remote Similarity NPC82635
0.6933 Remote Similarity NPC307965
0.6933 Remote Similarity NPC302041

  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 NPC309825 and all drugs/candidates.
●  The right table: Most similar clinical/approved drugs (Tc>=0.56 or Top200).

Similarity Score Similarity Level Drug ID Developmental Stage
0.7833 Intermediate Similarity NPD4219 Approved
0.75 Intermediate Similarity NPD6923 Approved
0.75 Intermediate Similarity NPD6922 Approved
0.7391 Intermediate Similarity NPD7143 Approved
0.7391 Intermediate Similarity NPD7144 Approved
0.7286 Intermediate Similarity NPD7150 Approved
0.7286 Intermediate Similarity NPD7151 Approved
0.7286 Intermediate Similarity NPD7152 Approved
0.726 Intermediate Similarity NPD6925 Approved
0.726 Intermediate Similarity NPD5776 Phase 2
0.7222 Intermediate Similarity NPD6942 Approved
0.7222 Intermediate Similarity NPD7339 Approved
0.72 Intermediate Similarity NPD7514 Phase 3
0.7162 Intermediate Similarity NPD7145 Approved
0.7162 Intermediate Similarity NPD7322 Clinical (unspecified phase)
0.7105 Intermediate Similarity NPD6902 Approved
0.7083 Intermediate Similarity NPD6926 Approved
0.7083 Intermediate Similarity NPD6924 Approved
0.7067 Intermediate Similarity NPD6929 Approved
0.6974 Remote Similarity NPD6931 Approved
0.6974 Remote Similarity NPD6930 Phase 2
0.6974 Remote Similarity NPD7332 Phase 2
0.6892 Remote Similarity NPD6933 Approved
0.6892 Remote Similarity NPD3701 Clinical (unspecified phase)
0.6825 Remote Similarity NPD342 Phase 1
0.6806 Remote Similarity NPD4243 Approved
0.68 Remote Similarity NPD6932 Approved
0.679 Remote Similarity NPD4751 Clinical (unspecified phase)
0.6757 Remote Similarity NPD8264 Approved
0.6753 Remote Similarity NPD7525 Registered
0.6716 Remote Similarity NPD368 Approved
0.6709 Remote Similarity NPD6695 Phase 3
0.6667 Remote Similarity NPD6898 Phase 1
0.6625 Remote Similarity NPD7338 Clinical (unspecified phase)
0.6623 Remote Similarity NPD6683 Phase 2
0.6622 Remote Similarity NPD4784 Approved
0.6622 Remote Similarity NPD4785 Approved
0.6543 Remote Similarity NPD6893 Approved
0.6533 Remote Similarity NPD5275 Approved
0.6533 Remote Similarity NPD4190 Phase 3
0.6494 Remote Similarity NPD5784 Clinical (unspecified phase)
0.6491 Remote Similarity NPD1799 Clinical (unspecified phase)
0.6471 Remote Similarity NPD4194 Approved
0.6471 Remote Similarity NPD4193 Approved
0.6471 Remote Similarity NPD4191 Approved
0.6471 Remote Similarity NPD4192 Approved
0.6438 Remote Similarity NPD4747 Approved
0.642 Remote Similarity NPD4786 Approved
0.6389 Remote Similarity NPD3621 Clinical (unspecified phase)
0.6386 Remote Similarity NPD7524 Approved
0.6386 Remote Similarity NPD7750 Discontinued
0.6375 Remote Similarity NPD3667 Approved
0.6351 Remote Similarity NPD5276 Approved
0.6329 Remote Similarity NPD7509 Discontinued
0.6301 Remote Similarity NPD4137 Phase 3
0.6279 Remote Similarity NPD7637 Suspended
0.6265 Remote Similarity NPD5279 Phase 3
0.622 Remote Similarity NPD3665 Phase 1
0.622 Remote Similarity NPD3666 Approved
0.622 Remote Similarity NPD3133 Approved
0.6216 Remote Similarity NPD6939 Phase 2
0.6216 Remote Similarity NPD4691 Approved
0.6216 Remote Similarity NPD6938 Clinical (unspecified phase)
0.6203 Remote Similarity NPD4195 Approved
0.6184 Remote Similarity NPD5733 Approved
0.6184 Remote Similarity NPD4687 Approved
0.6125 Remote Similarity NPD4748 Discontinued
0.6092 Remote Similarity NPD7087 Discontinued
0.6071 Remote Similarity NPD3618 Phase 1
0.6056 Remote Similarity NPD5325 Clinical (unspecified phase)
0.6047 Remote Similarity NPD4753 Phase 2
0.6047 Remote Similarity NPD5328 Approved
0.6 Remote Similarity NPD7645 Phase 2
0.5977 Remote Similarity NPD7136 Phase 2
0.5976 Remote Similarity NPD4223 Phase 3
0.5976 Remote Similarity NPD4221 Approved
0.5974 Remote Similarity NPD4058 Approved
0.5909 Remote Similarity NPD6079 Approved
0.5904 Remote Similarity NPD5362 Discontinued
0.5904 Remote Similarity NPD5332 Approved
0.5904 Remote Similarity NPD5331 Approved
0.5902 Remote Similarity NPD4265 Approved
0.5862 Remote Similarity NPD6051 Approved
0.5854 Remote Similarity NPD4790 Discontinued
0.5844 Remote Similarity NPD4732 Discontinued
0.5843 Remote Similarity NPD4202 Approved
0.5833 Remote Similarity NPD4197 Approved
0.5833 Remote Similarity NPD3668 Phase 3
0.5806 Remote Similarity NPD7640 Approved
0.5806 Remote Similarity NPD7639 Approved
0.5797 Remote Similarity NPD287 Approved
0.5783 Remote Similarity NPD4752 Clinical (unspecified phase)
0.5765 Remote Similarity NPD5329 Approved
0.5765 Remote Similarity NPD1696 Phase 3
0.5732 Remote Similarity NPD4822 Approved
0.5732 Remote Similarity NPD4819 Approved
0.5732 Remote Similarity NPD4821 Approved
0.5732 Remote Similarity NPD4820 Approved
0.5714 Remote Similarity NPD4629 Approved
0.5714 Remote Similarity NPD4788 Approved
0.5714 Remote Similarity NPD5210 Approved
0.5699 Remote Similarity NPD7638 Approved
0.5698 Remote Similarity NPD4694 Approved
0.5698 Remote Similarity NPD4693 Phase 3
0.5698 Remote Similarity NPD4623 Approved
0.5698 Remote Similarity NPD4690 Approved
0.5698 Remote Similarity NPD4519 Discontinued
0.5698 Remote Similarity NPD5280 Approved
0.5698 Remote Similarity NPD4689 Approved
0.5698 Remote Similarity NPD5690 Phase 2
0.5698 Remote Similarity NPD4688 Approved
0.5698 Remote Similarity NPD5205 Approved
0.5698 Remote Similarity NPD4138 Approved
0.5684 Remote Similarity NPD5211 Phase 2
0.5679 Remote Similarity NPD4271 Approved
0.5679 Remote Similarity NPD4268 Approved
0.5667 Remote Similarity NPD6399 Phase 3
0.5652 Remote Similarity NPD5220 Clinical (unspecified phase)
0.5652 Remote Similarity NPD4697 Phase 3
0.5652 Remote Similarity NPD5222 Approved
0.5652 Remote Similarity NPD5221 Approved
0.5647 Remote Similarity NPD6400 Clinical (unspecified phase)
0.5625 Remote Similarity NPD8262 Approved
0.5625 Remote Similarity NPD1346 Approved
0.5614 Remote Similarity NPD319 Phase 1

  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